European Journal of Radiology 83 (2014) 39–46

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European Journal of Radiology

journal homepage: www.elsevier.com/locate/ejrad

Cystic lung disease: Achieving a radiologic diagnosis

Beatrice Trotman-Dickenson ∗
Department of Radiology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, USA

a r t i c l e i n f o a b s t r a c t

Article history:
Received 12 June 2013
Received in revised form 6 November 2013
Accepted 29 November 2013
Keywords:
Lymphangioleiomyomatosis (LAM)
Tuberous sclerosis complex (TSC)
Pulmonary Langerhans histiocytosis (PLCH)
Birt–Hogg–Dubé (BHD)
Lymphocytic interstitial pneumonia (LIP)
Diffuse cystic lung disease represents a diverse group of uncommon disorders with characteristic appear-
ance on high resolution CT imaging. The combination of imaging appearance with clinical features and
genetic testing where appropriate permits a confident and accurate diagnosis in the majority of the dis-
eases without recourse for open lung biopsy. The mechanism of cyst development disease is unclear but
in some disorders appears to be related to small airways obstruction. These diseases are incurable, with
the exception of Langerhans cell histiocytosis which may spontaneously remit or resolve on smoking
cessation. Disease progression is unpredictable; in general older patients have a more benign disease,
while young patients may progress rapidly to respiratory failure. An understanding of the complications
of cystic lung disease and the appearance of disease progression is essential for the management of these
patients. A number of these disorders are associated with malignancy, recognition of the potential tumors
permits appropriate imaging surveillance. Due to the widespread use of CT, pulmonary cysts are increas-
ingly discovered incidentally in an asymptomatic individual. The diagnostic challenge is to determine
whether these cysts represent an early feature of a progressive disease or have no clinical significance. In
the elderly population the cysts are unlikely to represent a progressive disease. In individuals <50 years
further evaluation is recommended.
© 2013 Elsevier Ireland Ltd. All rights reserved.

1. Introduction association with small airways obstruction. In addition, there is a

Our knowledge of cystic lung disease has increased dramati-
cally in the last decade due to the widespread use of computed
tomography and the introduction of national and international reg-
istries for several of these rare conditions. The identification of
patients with asymptomatic cystic lung disease and serial scan-
ning in symptomatic patients has furthered our understanding of
cyst development, progression and prognosis of these diseases. The
purpose of this review is threefold: first, to define the demograph-
ics of these diseases; second, to describe the unique features of the
individual diseases, emphasize current knowledge; and third, to
provide an algorithm for achieving a confident diagnosis.
The most well-known of these rare entities are lymphangi-
oleiomyomatosis (LAM), pulmonary Langerhan’s cell histiocytosis
(PLCH) and Birt–Hogg–Dubé (BHD) [1–3]. LAM occurs in two forms,
sporadic LAM (S-LAM) and LAM associated with tuberous sclerosis
(TSC-LAM). S-LAM accounts for 85% of LAM cases on the National
Heart and Lung and Blood Institute LAM registry [4]. Lung cysts have
also been described in a variety of other diseases which include
lymphocytic interstitial pneumonia (LIP), hypersensitivity pneu-
monitis, light chain deposition disease (LCDD) and amyloidosis in
group of asymptomatic patients in whom the cysts are identified
as an incidental finding [5].
2. Demographics of cystic lung disease
2.1. Age
Cysts are known to occur with increasing frequency with
advancing years; however cysts should not occur in healthy indi-
viduals under the age of 50 years [6]. Cystic lung disease typically
affects adults in the 3rd to 4th decade. The peak incidence for PLCH
[7] and BHD is 20–40 years [8]. The median age for presentation
of LAM is 38 years [4]. LAM had been characterized as a disease of
premenopausal women. However, due to the increased detection
of subclinical disease by screening HRCT programs, LAM has now
been documented in post-menopausal women. Up to one-third of
patients registered in the NHLBI registry are post-menopausal and
individuals in their 8th decade have been diagnosed with LAM [4].
LIP has been reported in a wide age range of individuals from the
young to the elderly with a mean age of 50 years [9].

2.2. Gender

∗ Tel.: +1 617 732 6285; fax: +1 617 264 6802. LAM is almost exclusively a disease of women. The diagnosis
E-mail address: btrotmandickenson@partners.org of LAM is extremely unlikely in a male presenting with lung cysts.

0720-048X/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ejrad.2013.11.027
40 B. Trotman-Dickenson / European Journal of Radiology 83 (2014) 39–46
PLCH was initially reported as more common in men, but due to
increased smoking in women, there is no longer a gender bias. BHD
occurs with equal frequency in both men and women [10]. While
LIP is more common in women likely due to the association of LIP
with auto-immune disease [11].
2.3. Smoking
PLCH is a disease of smokers, current smokers or ex-smokers.
The diagnosis of PLCH is excluded in a nonsmoker. Complete remis-
sion of PLCH may occur on smoking cessation and in a significant
number of patients this is the only therapeutic intervention needed.
PLCH may also resolve spontaneously even in those who continue
to smoke. A variety of other smoking related pathologies including
desquamative interstitial pneumonia (DIP) and respiratory bron-
chiolitis associated interstitial lung disease (RB-ILD) maybe occur in
conjunction with PLCH [12]. The primary target in all these smoking
related lung diseases appears to be the terminal or respiratory bron-
chiole [13]. In some individuals with PLCH, the extent of RB-ILD/DIP
on lung biopsy maybe very extensive [14].
2.4. Clinical symptoms
Pneumothorax is the most common acute presentation of
cystic lung disease and shortness of breath the most common
chronic symptom. Spontaneous pneumothorax in a young, other-
wise healthy individual is most likely due to apical blebs. However
approximately 10% of patients with primary spontaneous pneu-
mothorax report a positive family history of pneumothorax [15].
Familial spontaneous pneumothorax is most commonly associated
with an inherited mutation of the folliculin gene with a 50 fold
increased risk of pneumothorax [8]. Recurrent pneumothorax in
a young female should raise concern for LAM. Spontaneous pneu-
mothorax was the sentinel event leading to diagnosis in 35% of
women with LAM [4].
Delayed diagnosis of cystic lung disease is common, particu-
larly in young women with sporadic LAM. The chest radiograph in
early disease appears normal or demonstrates lung hyperinflation.
Symptoms are nonspecific and often mimic asthma. Wheezing may
be seen in up to 50% of LAM patients [4] and approximately 25% of
patients with LAM have clinical response to bronchodilator inhaler
therapy [16].
Constitutional symptoms of fever, night sweats and anorexia are
the presenting complaint in one-third of patients with PLCH [17].
This clinical presentation needs to be distinguished from infectious
and malignancy etiologies. LIP may present with similar symptoms
or be asymptomatic.
2.5. Prognosis
The prognosis for cystic lung disease is variable and unpre-
dictable. In PLCH complete remission may occur. However,
approximately 10% of individuals with PLCH will progress to respi-
ratory failure and rapid progression to death may occur in months.
In PLCH, the degree of air flow obstruction is the best predictor of
adverse outcome. The median survival from diagnosis is 12.5 years
[18].
Survival for sporadic LAM is better than originally reported. Ear-
lier estimates of survival had ranged from 40% to 79%, 10-year
survival [19,20]. More recent studies document a 10-year sur-
vival of 91% from onset of symptoms [21]. The clinical course is
dependent on age of presentation. Patients who are diagnosed at
a younger age tend to have a more aggressive course. Presentation
following menopause tends to be more benign with longer survival.
TLCO and FEV1 are the best current indicators of disease progres-
sion and survival. Estrogen in the form of hormone replacement and
the contraceptive pill may promote progression of LAM and should
be avoided. Pregnancy has been associated with an irreversible
deterioration in lung function and an increased incidence of pneu-
mothorax [22]. The pulmonary disease in TSC-LAM tends to be
milder than in sporadic LAM. Prevalence of LAM in women with
TSC in a screening study was reported as 34% [23] representing a
10 fold higher prevalence compared to prior earlier studies suggest-
ing that an unrecognized sub clinical population of patients with
TSC are at risk of developing pulmonary complications.
In BHD, the lung disease demonstrates a slow rate of progres-
sion, and smoking appears to be associated with a more severe
disease compared to nonsmokers [24].
The natural history of the lung disease in LIP is extremely vari-
able; some patients recover completely without treatment while
others progress to respiratory failure and death. LIP is considered
a steroid responsive disease [11] but the response to therapy is
unpredictable. Approximately 33–50% die within 5 years of diag-
nosis and 5% of patients develop lymphoma [25].
2.6. Malignancy
Both TSC and BHD are associated with a variety of renal tumors.
The most common renal tumor in TSC is benign, an angiomy-
olipoma (AML) [26]. AML are more common in females and in
patient with a TSC2 gene mutation [26].
In BHD, renal tumors are often multiple, may be bilateral and
are noted at an earlier age (mean 50.7 years) than the general pop-
ulation. The tumors include chromophobe oncocytoma, renal cell
carcinoma and clear cell carcinoma [27]. Many of these tumors are
also seen in TSC. In TSC, the incidence of renal cell carcinoma is sim-
ilar to the general population but the tumors occur at a younger
age typically in the third decade as compared to the more usual
presentation in the fifth decade [28].
Patients with LAM are at an increased risk for the development
of meningiomas [29]. Progesterone therapy, a treatment used for
LAM is associated with an increase in growth of these tumors. Brain
MRI imaging is therefore recommended for all women with LAM
prior to commencing progesterone. Approximately 10% of patients
with TSC develop sub-ependymal giant cell tumors [30].
PLCH patients may be at increased risk of developing a malig-
nancy. Lymphoma, particularly Hodgkin’s disease, and multiple
myeloma have been reported in association with PLCH before, after,
or at the time of diagnosis [31].
Lymphoma is reported in individuals with LIP [25], but it
is unclear if this is a consequence of LIP or whether LIP was
manifestation of underlying lymphoma. Hematologic malignancy
particularly myeloma is found in the majority of patients with
LCDD. LCDD pulmonary disease should, therefore, be considered in
any patient with history of multiple myeloma or a lymphoprolifera-
tive disorder presenting with cystic lung disease [32]. The diagnosis
of LCDD may be confirmed by the presence of a monoclonal free
light chain, especially k in the serum or urine.
2.7. Genetics
Mutations in tumor suppressor genes have been identified in the
pathogenesis of TSC and BHD. Mutations in the tumor suppressor
genes TSC1 and TSC2 are associated with the development of LAM.
Mutations in the TSC2 gene arise more frequently than mutations in
TSC1 gene. TSC2 gene mutations are associated with greater disease
severity. Cystic lung disease is most commonly associated with the
TSC2 gene mutation [33].
Differentiating TSC-LAM and S-LAM disease relies on the identi-
fication of a family history of TSC and supporting clinical features of
TSC. TSC is an autosomal dominant disease and therefore 50% of off-
spring will inherit the disease. However 60% of TSC patients have no
 B. Trotman-Dickenson / European Journal of Radiology 83 (2014) 39–46 41

family history of the disease and represent a new germ line muta-
tion. Phenotypic variation maybe present even with families with
the same germ line mutation resulting in clinical variability. Only
10–20% of individuals have the classic combination of seizures,
mental retardation and adenoma sebaceum [23].
BHD is an autosomal dominant genodermatosis caused by a
mutation in the BHD gene which encodes for tumor suppressor
protein, folliculin [24]. This gene mutation is identified in 84%
of patients with BHD and in 64% of individuals with pulmonary
involvement as an isolated phenotype [34]. The majority of patients
with pulmonary cysts will have facial fibrofolliculomas. The inci-
dence of skin lesions increases after 20 years of age and then after
40 years of age [8]. Skin lesions, however, may be entirely absent.
There are no recognized genetic risk factors for developing PLCH.

2.8. Imaging findings

A pulmonary HRCT scan using a thin collimation, high spatial

reconstruction algorithm is recommended for the characterization
of cystic lung disease. The forme fruste of diffuse cystic lung dis-
ease is LAM. The diagnosis of LAM can often be confidently made by
imaging alone without recourse to open lung biopsy. PLCH is how-
ever a more difficult imaging diagnosis. The combination of nodules
and cysts needs to be differentiated from malignancy, infection and
other granulomatous diseases. In advanced PLCH, the large cysts
mimic bronchiectasis and in particular cystic fibrosis due to the
upper lobe predominance. Diseases which are associated with a
few scattered cysts are the most difficult to diagnose and to deter-
mine the clinical significance. There is a spectrum of diseases where
ground glass opacification is the primary manifestation and cysts
are a variable feature. The differential diagnosis is then determined
by the non-cystic features of the parenchymal lung disease. The
pertinent imaging features of specific cystic diseases will now be
reviewed.
2.9. CT findings of lymphangioleiomyomatosis
The cystic lesions of LAM are quite distinct [35]. They are
typically thin-walled, multiple well circumscribed and distributed
diffusely throughout the lungs with normal intervening lung
without lobar predominance (Fig. 1). These cysts range in size
from barely perceptible to several centimeters and in number from
a few scattered cysts to near complete replacement of the lung.
As the disease progresses, the cysts increase in size and number
but maintain their characteristic thin wall and rounded shape.
Fig. 2. HRCT of TSC-LAM demonstrating disease progression over a 7 year period
with an increase in size and number of cysts.
Eventually by end-stage disease, the lung may look very similar to
the end-stage disease of PLCH or emphysema (Fig. 2A and B).
Nodules are rarely seen in LAM. The incidence of nodular lesions,
either solid or ground glass, is approximately 9% and are more com-
monly seen in patients with TSC (12%) than S-LAM (1%) [36]. The
nodules vary in size from 1 to 10 mm and are usually upper lobe
predominant and often tiny and peripheral (Fig. 3). These nodules
represent a benign process, multifocal micronodular pneumocyte
hyperplasia (MMPH). MMPH occurs in both men and women with
TSC [37,38].
AML are common in both S-LAM and TSC-LAM. In TSC dis-
ease, the tumors are more often bilateral, tend to be larger and
are more prone to bleeding (Fig. 4A and B) [39]. Lymphatic abnor-
mality is common in S-LAM. Individuals may present with a
chylous pericardial or pleural effusions, thoracic and abdominal
lymphadenopathy, thoracic duct enlargement, and lymphangi-
oleiomyomas in the thorax and abdomen [40] (Fig. 5A and B).

Fig. 1. HRCT in a young woman with S-LAM demonstrates characteristic thin walled Fig. 3. HRCT is a patient with TSC reveals a few tiny ground glass nodules repre-
cysts with normal intervening lung. senting MNPH.
42 B. Trotman-Dickenson / European Journal of Radiology 83 (2014) 39–46
Fig. 4. (A) CT abdomen in a young female with cystic lung disease and TSC con-
firming the diagnosis of TSC-LAM reveals bilateral AML. (B) Huge bilateral AML
distorting the kidneys. Large AML lesions are prone to bleeding and maybe treated
by embolization.
Recent guidelines for the diagnosis of LAM have been pub-
lished by the European Respiratory Society LAM task force [41]. The
guidelines highlight diagnostic criteria and management including
current available treatment of the disease and its complications.
The diagnosis of LAM is classified as definite, probable and possible
LAM. The HRCT appearance of the lungs is classified as character-
istic or compatible with the diagnosis of LAM. The definition of a
characteristic HRCT appearance requires multiple >10 thin walled
cysts with normal or increased lung volumes without significant
other interstitial abnormality. The definition of compatible HRCT
findings is the appearance of typical cysts but few in number, >2
but less than 10 cysts. A definite diagnosis without recourse to
open lung biopsy requires a characteristic or compatible pulmonary
HRCT and lung biopsy with appropriate pathological features or a
characteristic pulmonary HRCT and any one of the following: renal
angiomyolipoma, thoracic and or abdominal chylous effusion, lym-
phangioleiomyoma, lymph node biopsy confirming LAM or definite
or probable TSC. A probable diagnosis is made with a characteristic
lung CT and compatible clinical history or a compatible HRCT with
any of the following: AML, thoracic and or abdominal chylous effu-
sion. A possible diagnosis is CT evidence of cystic lung disease and
no other clinical features. A follow up CT study demonstrating an
increase in size and number of cysts makes the diagnosis of LAM
more likely.
Fig. 5. (A) CT demonstrates a moderate chylous pericardial effusion and bilateral
small chylous pleural effusions in a patient with S-LAM. The distal thoracic duct is
dilated. (B) Same patient, CT abdomen shows a large retroperitoneal lymphangi-
oleiomyoma.
The Task Force also made recommendations for evaluation of
patient with known TSC. Females with TSC should be screened for
lung cysts at the age of 18 years and if negative again at 30–40
years. If persistent respiratory symptoms develop, scanning should
be performed as clinically appropriate. Screening for lung disease
in asymptomatic male patients with TSC is not recommended as
LAM almost exclusively affects females.
Recommendations were also made for evaluating female
patients presenting with AML. In a female with unilateral AML, pul-
monary CT scan should be considered for identification of LAM. In
a female with bilateral AML, TSC screening should be performed in
addition to pulmonary imaging. All patients newly diagnosed with
LAM should have abdominal pelvic imaging as abdominal pathol-
ogy is common [35].
Brain imaging is recommended for all patients with TSC and in
women with S-LAM prior to treatment with progesterone. Patients
with TSC should undergo annual MRI studies until 21 years of
age then every 2–3 years to diagnose and monitor giant cell
tumors.
Screening for serum VEGF-D levels (a lymphangiogenic growth
factor) is a useful marker for the identification of LAM in patients
with cystic lung disease and may also have prognostic signif-
icance. A serum VEGF-D level of >800 pg ml in a patient with
characteristic cystic lung appearance has been shown to be diag-
nostically specific for S-LAM and identifies LAM in females with TSC
[42].
 B. Trotman-Dickenson / European Journal of Radiology 83 (2014) 39–46
Fig. 6. CT chest images from a PETCT in a 40 year smoker with recurrent Hodgkin’s
disease demonstrates multiple small nodules and cavities representing biopsy
proven PLCH.
2.10. CT findings in pulmonary Langerhans cell histiocytosis
The most common manifestations of PLCH are cysts and nodules
(Fig. 6). The cysts and nodules demonstrate characteristic upper
lobe predominance with sparing of the costophrenic angles [43].
The stage and severity of the lung disease is determined by the size
and number of the cysts and nodules. As the disease progresses,
the nodules disappear and the cysts enlarge (Fig. 7A and B). Unlike
LAM, the diagnosis of early PLCH maybe suspected on the chest
radiograph as nodules is more readily identified than thin walled
Fig. 7. PLCH in a young male smoker demonstrates characteristic distribution of
PLCH. (A) HRCT images reveal the upper lobe distribution of the cystic lung disease.
(B) HRCT images through the lung bases demonstrate sparing of the costophrenic
sulci by the cystic disease.
43
cysts. In PLCH, the cysts vary in size and wall thickness. The wall
thickness of the cysts ranges from barely perceptible to several mil-
limeters in thickness and is dependent on the degree of nodule
cavitation. The cyst walls often appear irregular. Typically round in
configuration, larger cysts however may demonstrate branching or
septations and resemble bronchiectasis (Fig. 8). The size of the cysts
appears dependent on the severity of air flow obstruction from a
check ball valve mechanism. Cysts of differing appearance may be
seen at the same time.
By end stage disease, the chest radiograph resembles that of
emphysema due to the severe destruction of the lung parenchyma
and resolution of nodules (Fig. 9). The key to the diagnosis of PLCH
relies on the patient’s age; the patient is usually too young for such
severe smoking-related emphysema. Although alpha-1-antitrypsin
deficiency related emphysema is found in a similar young age
group, the lower lobe predominance of this type of emphysema
distinguishes alpha-1-anti-trypsin deficiency from PLCH.
Pericystic opacification and ground glass opacities are uncom-
mon manifestations of PLCH (Fig. 10). DIP occurring with PLCH
needs to be differentiated from other causes of diffuse ground glass
opacification (Fig. 11). Lymphadenopathy and pleural effusions are
occasionally seen.
The diagnosis of PLCH is highly likely in a young smoker with
evidence of pulmonary nodules and cysts with an upper lobe dis-
tribution with sparing of the costophrenic sulci. If the disease
regresses on cessation of smoking, the diagnosis is confirmed. If
the disease progresses, or there is initial diagnostic uncertainty
a bronchoalveolar lavage should be considered. The presence of
CD1a-reactive cells >5% within the lavage fluid confirms the diag-
nosis of PLCH.
A CD1a count of <5% in the lavage fluid is nonspecific and a
trans-bronchial biopsy (TBB) should be considered [44,45]. How-
ever the routine use of TBB is not recommended due to the low
sensitivity. An open lung biopsy is more likely to be definitive. If
the open lung biopsy is non-diagnostic, follow-up CT in 3 months
is recommended.
2.11. CT findings in Birt–Hogg–Dubé
The majority of patients with BHD have pulmonary cysts [10]. In
BHD, the cysts are thin walled, sometimes septated and varying in
size from a few millimeters to several centimeters [24,46,47]. Many
of the cysts are irregular in shape; the majority of cysts are round
or oval. The cysts are often subpleural in location and are predo-
minately lower medial zone in location. The cysts frequently abut
the proximal lower lobe, proximal pulmonary arteries and veins.
Nodules are not seen. The typical presentation is a patient with
skin lesions and a history of recurrent and familial pneumothorax
(Fig. 12). However patients with BHD may not have all three man-
ifestations of the syndrome (pulmonary, renal and dermatological
lesions), cysts maybe the only finding, or the cysts may proceed the
development of renal and skin abnormalities [8] .The frequency of
pneumothorax in BHD is most common between 20 and 40 years
of age and less common after the age of 40, suggesting that older
patients may have a less severe form of BHD [8]. Approximately 90%
of patients with BHD will have their first pneumothorax before the
age of 50 years [10].
Patients presenting with pneumothorax, pulmonary cysts, skin
and renal lesions may have BHD or TSC. BHD is more likely to be the
cause of the cystic lung disease if there is a strong family history of
recurrent pneumothorax. The presence of AML favors TSC disease.
Renal carcinoma may be found with either disease process.
Dermatology referral for evaluation of the skin lesions and clin-
ical evaluation of family members for skin and renal lesions is
helpful in differentiating between the two entities. Testing for the
appropriate gene mutation may confirm the diagnosis.
44 B. Trotman-Dickenson / European Journal of Radiology 83 (2014) 39–46

Fig. 8. 30 year female smoker with PLCH for 5 years. (A) HRCT of the upper lobes reveals multiple cysts of varying size and shape. Several of the cysts are tubular and to have
septations. A few tiny scattered right upper lobe peripheral nodules are demonstrated. (B) Coronal image reveals upper lobe predominance of the cysts. Overlapping cysts
resembles cystic bronchiectasis. (C) Sagittal image. The cystic areas are seen to be rounded or tubular without evidence of branching and therefore represent parenchymal
cysts and not cystic bronchiectasis.

In the absence of skin and renal lesions, the differential diag-
nosis for pulmonary cysts includes LAM, PLCH and LIP. The cysts
in BHD tend to be variable in size and shape, while the cysts in
LAM are uniform in shape and size and typically more numerous.
In PLCH the cysts are upper lobe predominant and in BHD the cysts
are lower lobe predominant. In LIP, the cysts are usually found in
combination with ground glass opacities and in the presence of an
immunological disease.
2.12. CT findings in lymphocytic interstitial pneumonia
LIP is a benign lymphoproliferative disorder most commonly
seen in individuals with autoimmune disease (Sjogren’s), acquired
immune deficiency syndrome or Castleman’s disease. LIP is char-
acterized by a combination of ground glass opacification, poorly

Fig. 9. HRCT appearance of end stage lung disease due to PLCH is indistinguishable
from other causes of severe cystic lung disease. If AML are present a diagnosis of
LAM can be made. If the individual is a nonsmoker then PLCH and emphysema can
be excluded. If the individual is a smoker and the cysts involve costophrenic angle, Fig. 10. Pericystic ground glass opacification is an uncommon manifestation of PLCH
PLCH is then unlikely. representing the “reactive” component of the disease.
 B. Trotman-Dickenson / European Journal of Radiology 83 (2014) 39–46 45

Fig. 11. PLCH complicated by another smoking related lung disease, DIP. The diffuse
upper lobe ground glass opacification of DIP needs to be distinguished from pneu-
mocystis pneumonia. However patients with PLCH maybe at risk from pneumocystic
pneumonia due to the common use of steroid therapy.

defined centrilobular nodules, interlobular septal thickening,

thickening of the bronchovascular bundles and scattered cysts
(Fig. 13A and B). The cysts in LIP are typically large, usually few in
number, often sub pleural in location and maybe the sole manifes-
tation of this disease [48]. Mediastinal and hilar lymphadenopathy
is present in the majority of patients.
The diagnosis of LIP should be considered in a patient with lung
cysts and an immunological abnormality. A few scattered cysts
in a patient with Sjogren’s syndrome are very likely due to LIP
(Fig. 14) [49]. The cystic disease of BHD may appear similar, but
the majority of these patients will have a family history of pul-
monary cysts and skin lesions. Also BHD is not associated with
immunological disease. In a patient with HIV disease, the findings Fig. 13. HRCT in a male with HIV disease and LIP confirmed by open lung biopsy.
(A) HRCT image through the upper lobes reveals a few cysts of varying size and
of ground glass opacities, cysts, and interlobular septal thickening
several patchy areas of ground glass opacification. (B) HRCT image through the lung
raises the possibility of LIP [50] or pneumocystis jiroveci pneu- bases demonstrates multifocal ground glass opacification with a bronchovascular
monia. Both conditions may present with fever and cough and distribution and minimal septal thickening. Pneumocystic pneumonia needs to be
the diagnosis of LIP usually relies on the exclusion of pneumocys- considered even though the ground glass is lower lobe predominant. Cysts maybe
tis pneumonia. Ground glass opacities and cysts are a feature of seen in both conditions. Chronicity of the appearance will help differentiate LIP from
pneumonia.
sub-acute hypersensitivity pneumonitis [51]; however, interlob-
ular septal thickening and lymphadenopathy are not. Air trapping

Fig. 14. HRCT in a young woman with Sjögren’s syndrome presenting with chronic
dyspnea. A few thin walled cysts only are identified. The appearance is consistent
with LIP. Her respiratory symptoms may be due to small airways diseases which is
associated with this autoimmune disorder.

within secondary pulmonary lobules is a feature of sub acute hyper-

sensitivity and is not seen in LIP. The diagnosis of LIP often requires
confirmation by transbronchial or open lung biopsy.

Fig. 12. Coronal CT image in a patient with BHD presenting with a spontaneous
left sided pneumothorax. A few scattered cysts are identified, confined to the lower
lobes.
3. Conclusion
Cystic lung diseases are of two types; diffuse cystic lung dis-
ease and diseases characterized by a few cysts only. A confident
46 B. Trotman-Dickenson / European Journal of Radiology 83 (2014) 39–46
diagnosis is more readily attained with the former group. Cysts
detected as an incidental finding on pulmonary imaging are the
most problematic group to diagnose and most difficult to deter-
mine the significance of the process. The cysts may develop as the
sequela of chronic small airways disease [5]. Often, it may be impos-
sible to achieve a confident imaging diagnosis. In general, scattered
cysts have more clinical significance in a young individual than in
the elderly. In an asymptomatic elderly individual, cysts can usually
be clinically ignored; the cysts may represent the aging process and
or limited small airways disease. In a young female however, the
cysts may represent LAM and abdominal imaging should be per-
formed for identification of AML and lymphatic abnormalities. In
the absence of abdominal findings, short term CT follow up imag-
ing is recommended to determine if the cysts increase in size and
number suggesting probable LAM. Family history is an important
component of evaluation of cystic lung disease and the diagnosis
may subsequently be confirmed by genetic testing. A number of
cystic lung diseases are associated with malignancy, in particular
renal lesions and it is important to recognize these associations and
screen for tumors.
Conflict of interest
No conflicts of interest by author or author’s institution.
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