ipf or non ipf interstitial lung diseases
TRANSCRIPT
IPF or Non-IPF Interstitial Lung Diseases
By
Gamal Rabie Agmy , MD , FCCP Professor of Chest Diseases ,Assiut University
• Interstitial compartment is the portion of the lung sandwiched between the epithelial and endothelial basement membrane
• Expansion of the interstitial compartment by inflammation with or without fibrosis – Necrosis
– Hyperplasia
– Collapse of basement membrane
– Inflammatory cells
What is the Pulmonary
Interstitium?
The interstitium of the lung is not normally visible radiographic-
ally; it becomes visible only when disease (e.g., edema,
fibrosis, tumor) increases its volume and attenuation.
The interstitial space is defined as continuum of loose
connective tissue throughout the lung composed of three
subdivisions:
(i) the bronchovascular (axial), surrounding the bronchi,
arteries, and veins from the lung root to the level of the
respiratory bronchiole
(ii) the parenchymal (acinar), situated between the alveolar
and capillary basement membranes
(iii) the subpleural, situated beneath the pleura, as well as in
the interlobular septae.
The Lung Interstitium
Secondary pulmonary lobular
anatomy
The terminal bronchiole in the center
divides into respiratory bronchioles with
acini that contain alveoli.
Lymphatics and veins run within the
interlobular septa
Centrilobular area in blue (left)
and perilymphatic area in yellow
(right)
Ideal ILD doctor
Radiologist
Pathologist
Pulmonologist
DPLD of known
cause (e.g. drugs,
dust exposure,
collagen vascular
disease)
Idiopathic
interstitial
pneumonias
Granulomatous
DPLD (e.g.
sarcoidosis)
Other forms of DPLD
(e.g. LAM, HX,
eosin. pneum. etc.)
Diffuse Parenchymal Lung Disease
IIP other than
idiopathic
pulmonary fibrosis
Idiopathic
pulmonary
fibrosis (IPF)
Desquamative interstitial
pneumonia (DIP)
Acute interstitial
pneumonia (AIP)
Lymphocytic interstitial
pneumonia (LIP)
Nonspecific interstitial
pneumonia (NSIP)
Cryptogenic organising
pneumonia (COP)
Respiratory bronchiolitis/
Interst. lung dis. (RBILD)
Clinical Categorisation of
Idiopathic Interstitial
Pneumonias
7 histological categories
• Usual interstitial pneumonia (UIP)
• Nonspecific interstitial pneumonia (NSIP)
• Organising pneumonia (OP)*
• Diffuse alveolar damage (DAD)
• Desquamative interstitial pneumonia (DIP)**
• Respiratory bronchiolitis (RB)
• Lymphocytic interstitial pneumonia (LIP)
* previously BOOP ** previously AMP
Correlation with HRCT patterns
7 clinical-radiological-pathological categories
ATS/ERS International Multidisciplinary Consensus Classification of the
Idiopathic Interstitial Pneumonias, AJRCCM Vol 165. pp 277-304, 2002
UIP
+ NSIP
+ OP
+ DAD
+
DIP
+ RB
+
LIP
+
=
IPF
=
NSIP =
COP
=
AIP =
DIP
=
RB-ILD =
LIP
Histology:
• Heterogeneous appearance
ü(hardly any inflammation)
• Temporal heterogeneity
Old + new fibrosis (fibroblastic foci)
IPF/UIP „disease status‟
Non-specific interstitial pneumonia ’IIP-NSIP cellular / fibrotic variant’
• temporal uniformity on biopsy
• no / few fibroblastic foci
• fine reticulation
• ground glass
Cryptogenic organising
pneumonia
(BOOP)
• patchy consolidations (95%)
• perilobular opacity (50%)
Ujita, Radiology 2004; 232: 757-61
Congestion & oedema
Exudative phase
Acute interstitial
pneumonia
acute onset, with systemic features: idiopathic ARDS
granulocytes + occasional lymphocytes; debris
survival from diagnosis often days despite mechanical support
Respiratory bronchiolitis associated
interstitial lung disease
cigarette smoker obstructive or restrictive lung function AM with smoker’s inclusions on BAL
Desquamative interstitial pneumonia (AMP)
smoker BAL: AM+++N+E+L
LIP Lymphocytic interstitial pneumonia
AIDS
lymphoproliferative
rheumatological
idiopathic (rare)
lymphocytes on BAL
Correct IIP diagnoses need teamwork
and experience
Flaherty KR, AJRCCM 2004;170:904-10
Pulmonologist Radiologist
Pathologist
Diagnosis
Practical issues • Clinical setting with regular meetings
of key specialists
• Not all IIP cases are classifiable:
„non-classifiable interstitial
pneumonias‟ (8th category)
• NSIP is an area of important
uncertainty (NSIP ~ provisional
category) > 50% of inter-observer variation between pathologists
and radiologists relate to the diagnosis of NSIP
Nicholson AG, Thorax 2004; 59:500-5 // Aziz ZA, Thorax 2004; 59:506-11
ATS/ERS INTERNATIONAL MULTIDISCIPLINARY CONSENSUS CLASSIFICATION OF IDIOPATHIC
INTERSTITIAL PNEUMONIAS
General Principles and Recommendations
Co-chairs: William D. Travis, M.D.
Talmadge King, Jr. M.D.
Am J Respir Crit Care Med 2002; 165: 277
Classification
Diagnostic
Approach
According to
ATS/ERS Statement
2002
Roles of Clinicians, Radiologists and Pathologists
Radiologists Pathologists
Clinicians (Pulmonologists)
•History •Exposure •Drugs
•Symptoms & Signs
•Should know, identify and report pattern-specific features
•Systemic Diseases (CVD)
•Age
•Should know, identify and report pattern-specific features
Diagnostic Process in DPLD
History, physical examination,
chest radiograph, lung function tests
Not IIP e.g. assoc. collagen vascular disease,
environmental, drug-related, etc.
Possible IIP
HRCT
History: Onset of Pulmonary Symptoms
ACUTE SUBACUTE CHRONIC
• COP
• AIP
• Ac.Eos.Pn.
• Acute HP
• Drug-induced
injury
• COP
• Subacute HP
• Chron.Eos.Pn.
• Drug-induced ILD
• IPF
• NSIP
• DIP/RBILD
• chronic HP
• CVD-associated ILD
• Asbestosis, Silicosis
Sarcoidosis
Histiocytosis X
Lymphangioleiomyomatosis
IPF
HRCT
Confident CT
diagnosis of IPF with
consistent clinical
features
Atypical clinical
or CT features
for IPF
If non-diagnostic
Features diagnostic
of another
DPLD e.g. HX
Suspected
other DPLD
Surgical lung biopsy
TBBx, BAL or
other relevant
test
TBBx or
BAL?
UIP NSIP RB DIP DAD OP LIP non-IIP confirmed
IPF without surgical biopsy (ATS/ERS Statement 2000)
Major Criteria (all required)
• exclusion of known causes
of ILD
• abnormal PFT including restriction and impaired gas exchange
• bibasilar reticular abnormalities with minimal ground glass on HRCT
• TBB or BAL showing no features to support an alternate diagnosis
Minor criteria (3 of 4 required)
• age > 50 yr
• insidious onset of otherwise unexplained dsypnea on exertion
• duration of illness > 3
months
• bibasilar inspiratory crackles
(velcro-type)
Idiopathic Pulmonary Fibrosis:
typical CT features
• Subpleural/basal
• Fine reticular
• Honeycombing
• Little/no groundglass
HRCT Criteria of IPF
1-reticular abnormality and/or traction bronchiectasis with basal and peripheral predominance
2-honeycombing with basal and peripheral predominance
3-atypical features are absent – Micronodules are not present – peribronchovascular nodules are not present – consolidation is not present – ground glass attenuation, if present, is less extensive
than reticular opacity – mediastinal adenopathy, if present, is not extensive
enough to be visible on chest X-ray
Definite IPF: all 3 are met
Probable IPF: 1 and 3 are met
Accuracy of Clinical & Radiological Diagnosis of IPF
• 59 patients with surgical biopsies
• clinical diagnosis or radiological diagnosis
• clinical diagnosis of IPF
- 97% specific
- 62% sensitive
• HRCT diagnosis of IPF
- 90% specific
- 79% sensitive Raghu et al, 1999
Pitfalls with CT
Technical Issues
• HRCT vs. conventional CT
• Gravity effects
• Expiration
Conventional CT vs HRCT
HRCT Conventional
CT
IPF inverted Position
Bronchiolitis: Mosaic Pattern
Inspiration Exspiration
Role of BAL in IPF
• Increase in neutrophils +/-
eosinophils (in 90%) suggests a fibrosing process: IPF, collagen/vascular disease, asbestosis
• A lone increase in lymphocytes is uncommon, exclude: sarcoidosis, EAA, BOOP, NSIP, LIP
• BAL may reveal alternative specific diagnoses: malignancy, infections, eosinophilic pneumonia, histiocytosis X, alveolar proteinosis
HRCT
Confident CT
diagnosis of IPF with
consistent clinical
features
Atypical clinical
or CT features
for IPF
If non-diagnostic
Features diagnostic
of another
DPLD e.g. HX
Suspected
other DPLD
Surgical lung biopsy
TBBx, BAL or
other relevant
test
TBBx or
BAL?
UIP NSIP RB DIP DAD OP LIP non-IIP confirmed
When do we need surgical biopsy in idiopathic interstitial pneumonias?
• IPF-like CT pattern and age > 50 yrs: no
• COP with characteristic clinical/CT/BAL/TBLB features: no
• RBILD/DIP?
• Other IIP entities: yes
Surgical Lung Biopsy – special risk in IPF
• 60 pat with UIP (46 idiopathic, 14 associated with collagen/vasc dis) from Mayo Clinic 1986 - 1995
• 10/60 (=17%) died within 30 days after surgical biopsy
3/16 (19%) after VATS
7/44 (16%) after thoracotomy and biopsy
• All 10 who died had IPF, 5 of these were biopsied for accelerated progress
Utz et al, ERJ 2001; 17: 175
Mortality and Risk factors for Surgical Lung Biopsy in IIP
• 200 pat. with IIP (140 IPF, 46 NSIP, 14 COP), retrospective study
• 4.3% died within 30 days after surgical biopsy,
no difference between VATS or OLB no difference between IPF and other IIPs
• Biopsy at time of acute exacerbation: mortality 29% vs 3%
• DLCO<50%: mortality 11% vs 1.4%
Park JH et al, Eur J Cardiothorac Surg 2007
Key histopathological features - UIP Pattern
• Dense fibrosis and honeycombing
• Fibroblastic foci prominent
• Patchy, heterogeneous pattern
• Subpleural, paraseptel
distribution
Fibroblastic
Foci
UIP pattern
Courtesy T.V. Colby
Nonspecific Interstitial Pneumonia (NSIP) Pattern
• Preserved architecture, variable fibrosis and cellularity
• Few fibroblastic foci
• Temporally homogenous
• Inconsistent distribution
Cellular NSIP
Desquamative Interstitial Pneumonia (DIP) Pattern
• Intra-alveolar macrophage accumulation
• No fibroblastic foci
• Uniform involvement
• Diffuse distribution
Pulmonologists’ Problems with Pathologists
• No description of pattern-specific
features
• No final report of the pattern
How to make the diagnosis of an IIP entity?
• Not by histology alone!
• To define a disease as idiopathic, all known associated conditions and causes have to be excluded.
• This cannot be done by the pathologist – none of the histologic patterns are specific for the idiopathic entities but also seen in associated conditions.
• The final diagnosis can only be made in a clinical/radiologic/pathologic synopsis.
Controversy and Confusion with the term UIP
• Clinicians have used the name of the histological patterns for the clinical diagnosis
• Radiologists use the term UIP for the HR-CT pattern
• What is UIP? - A histological (or CT/or BAL) pattern, not a clinical diagnosis
• Is UIP the same as IPF? -- No! (Histological UIP pattern can be seen in other ILDs) • Why not call IPF “idiopathic UIP“?
Clinical conditions associated with UIP pattern
• Idiopathic pulmonary fibrosis/crytogenic fibrosing alveolitis
• Collagen vascular disease
• Drug toxity
• Chronic hypersensitivity pneumonitis
• Asbestosis
• Familial idopathic pulmonary fibrosis
• Hermansky-Pudlak syndrom
Prognosis of Fibrotic Interstitial Pneumonia
IIP vs CVD-IP Idiopathic UIP vs CVD-UIP vs
Idiopathic NSIP vs CVD-NSIP Park JH, et al. AJRCCM 2007; 175: 705
(n = 362; IIP 269, CVD 93)
Clinical conditions associated with NSIP pattern
• No detectable cause (idiopathic NSIP)
• Collagen vascular disease
• Hypersensitivity pneumonitis
• Drug-induced pneumonitis
• Infection
• Immunodeficiency including HIV
infection
Chronic bird fancier‘s lung: histopatho-logical and clinical correlation
Ohtani et al 2005
• BOOP 2
• NSIP, cellular 5
• NSIP, fibrotic 8
• UIP-like 11
Total n = 26
recurrent episodes,
good outcome
insidious onset,
unfavorable outcome
Controversy
• Do NSIP and DIP reflect early stages of
the IPF/UIP patients ?
• Majority of researchers believe now that
these three histologic patterns also
reflect three different entities
DIP
Initial 24 months later
Ryu 2005
Controversies with RBILD/DIP
• Should RBILD be included in the IIP„s?
100% are cigarette smokers, so a disease of known aetiology!
• DIP is not exclusively seen in smokers, 15% are nonsmokers
Ryu et al. Chest 2005,127:178
Is histopathology still the gold standard for diagnosis?
Problems:
• Sampling error
• Interoberserver variation between histopathologists
Discordant Lobar Histology
Lower lobe: UIP Middle lobe: NSIP
Histopathologic Variability: Survival Depends on the UIP Pattern
Cumulative
proportion
surviving
Years CP1047154-2 Flaherty et al: AJRCCM, 2001
NSIP
Discordant UIP
Concordant UIP
(n=30)
(n=28)
(n=51)
Is histopathology still the gold standard for diagnosis?
Problems:
• Sampling error
• Interoberserver variation between histopathologists
Rating of κ scores
Landis JR, Koch GG. 1977
agreement κ score
• perfect
• substantial
• moderate
• fair
• slight
• poor
> 0.8
0.6 - 0.8
0.4 - 0.6
0.2 - 0.4
0.0 - 0.2
= 0.0
Interobserver variation between histopathologists
In a recent study, 133 biopsies were
assessed by 10 experienced specialist
histopathologists
The interobserver agreement was barely
clinically acceptable: Kappa coefficient of
agreement only 0.4
Nicholson et al, Thorax 2004
Kappa coefficients of agreement between 10 pathologists (Nicholson 2004)
Diagnosis Lobar
diagnosis
(n=98)
Final diagnosis
(n=48)
UIP 0.40 0.49
NSIP 0.32 0.32
DIP 0.67 0.71
OP 0.59 0.67
EAA 0.39 0.35
Sarcoidosis 0.76 0.82
Overall 0.39 0.43
Ideal ILD doctor
"Pulmo-radio-pathologist"
Combining 3 brains in one
head!
HRCT in the Idiopathic
Interstitial Pneumonias
• A radiologist‟s view of the spectrum
of IIPs
• HRCT sketches of the IIPs
• Issues: – “Added value” signs on HRCT – Observer variation – Overlap lung disease
Idiopathic interstitial pneumonias a perception / definition:
“A group of disorders with a shifting histopathological classification, unclear clinical significance, and largely unmemorable imaging features.”
E.G.Journeyman 2001
IIPs included in the current classification:
• Usual interstitial pneumonia (UIP)
• Non-specific interstitial pneumonia (NSIP)
• Respiratory Bronchiolitis (RB-ILD)
• Desquamative interstitial pneumonia (DIP)
• Diffuse alveolar damage / Acute interstitial
pneumonia (AIP)
• Organizing pneumonia (OP)
• Lymphoid interstitial pneumonia (LIP)
International Consensus (ATS/ERS) Classification of Idiopathic Interstitial Pneumonias 2002
Organizing pneumonia
Respiratory Bronchiolitis-ILD
Lymphoid interstitial pneumonia
Acute interstitial pneumonia
UIP: HRCT appearances
• Subpleural basal honeycombing – May be component of ground glass opacification
and fine reticular elements
– Volume loss and traction bronchiectasis
– Enlarged mediastinal lymph nodes
UIP
basal subpleural honeycombing*
*not merely reticular pattern, check density within cystic air spaces
sarcoid
UIP
Accelerated UIP
5 weeks later
Differential diagnosis for rapid
development of widespread
ground glass opacification in IPF:
• Accelerated phase of the disease
• Supervening heart failure (oedema)
• Opportunistic infection
• Drug reaction – esp. novel drugs
• (Spurious – expiratory CT)
Added value features on “UIP
HRCT”
• Lung cancer
– n.b. differential of mass-like TB
• Pulmonary oedema
• “Not UIP”
– Hypersensitivity pneumonitis
– Centrilobular emphysema / presbyteric
lung
NSIP…
NSIP: initial reports of CT
spectrum of findings: • Ground glass opacification with or
without areas of consolidation
• Linear opacities and reticular pattern, but honeycombing limited or absent
• Lower zone predominance, may be subpleural predilection
Park et al Radiology 1995;195:645 Hartman et al Radiology 2000;217:701
NSIP
A fibrosing lung disease in which ground glass is predominant and honeycombing is minimal or absent, often with a peripheral basal distribution
1 Harrison et al Respir Med 1989;83:403-14
2 Wells et al Am J Respir Crit Care Med 1994;149:1583
• 1989: No histological difference between CFA and fibrosing alveolitis in systemic sclerosis1.
• 1994: Fibrosing alveolitis associated with systemic sclerosis has a better prognosis than lone CFA2.
• 1992/4: Kitaichi, Katzenstein describe NSIP
• 1997: Chan et al paper in Thorax
• 1998 – : Clinicians, radiologists recognize NSIP and its prognostic implications
Some history:
“systemic sclerosis type”
“lone CFA type”
Chan et al. Thorax 1997;52:265
n.b. Subsequent pathological studies have shown that NSIP is the most prevalent pattern in systemic sclerosis associated pulmonary fibrosis
NSIP Gr 3 (fibrotic)
NSIP Gr 1 (cellular)
UIP
NSIP
Hmmm…….
NSIP with superimposed centrilobular emphysema
• Cigarette smoking
• Ageing (presbyteric) lung
“expected”
changes
Cigarette smokers
2x cigarette smokers (<65 years old)
80 year old
73 year old
• NSIP (fibrotic)
• Chronic hypersensitivity pneumonitis
• Fibrotic sarcoidosis
• Organizing pneumonia admixed fibrosis
If not UIP (n.b. non-typical HRCT UIP) consider:
UIP – The most frequently encountered and lethal IIP
– Characteristic HRCT features in approximately 50%
– Biopsy unnecessary when HRCT and clinical
features typical
NSIP – Better prognosis than UIP
– Commonest IIP in connective tissue disease
– HRCT pattern recognisable but not specific (may be
a front for UIP)
Radiologists’ Observer Variation
Thorax 2004;59:506
Interobserver variation between pathologists
in diffuse parenchymal lung
AG Nicholson, BJ Addis1, H Bharucha2, CA Clelland3, B Corrin, AR
Gibbs4, PS Hasleton5, K Kerr6, NB Ibrahim7, S Stewart8, W Wallace9,
and AU Wells10.
Departments of Histopathology, Royal Brompton Hospital, Southampton
General Hospital1, Royal Victoria Hospital, Belfast2, John Radcliffe
Infirmary3, Llandough Hospital4, Wythenshawe Hospital5, Aberdeen
Royal Hospitals6, Frenchay Hospital 7, Papworth Hospital8, Edinburgh
Royal Hospital9, and Department of Medicine10, Royal Brompton
Hospital, UK.
Thorax 2004;59:500
Kappa values for histopathological diagnosis
[<0.4 = poor, 0.4-0.6 = satisfactory, 0.6-0.8 = good, >0.8 = excellent]
DIAGNOSIS (n=133) KAPPA COEFFICIENT FOR LOBAR Dx
UIP 0.42
NSIP 0.29
OP 0.57
Hypersensitivity pneumonitis 0.36
Sarcoidosis 0.76
Other diffuse lung diseases 0.41
Overall kappa value = 0.38 for lobar diagnoses
“The only use of a diagnostic test is to reduce uncertainty”
EJ Potchen 1998
Change in diagnostic
perception: 1st choice diagnosis changed in
51% of cases after HRCT
• Significant increase in diagnostic
confidence
• Overall kappa for 1st choice diagnosis
before HRCT 0.47 (moderate)
after HRCT 0.72 (good)
Aziz et al Radiology 2006;238:725
Weighted kappa coefficients of individual disease categories for the entire cohort before and after HRCT
Kw before HRCT Kw after HRCT
Idiopathic pulmonary fibrosis 0.58 0.89
Non-specific interstitial pneumonitis 0.20 0.63
Sarcoidosis 0.68 0.88
Hypersensitivity pneumonitis 0.65 0.67
Cryptogenic organizing pneumonia 0.51 0.71
Smoking related-interstitial lung disease 0.30 0.46
Interstitial pneumonias secondary to 0.69 0.78
connective tissue disease
“OVERLAP LUNG DISEASE” IN THE CONTEXT OF THE IIPs
When HRCT shows several patterns, it may be that:
– Single disease has more than one HRCT
pattern
– More than one disease present
– Two phases of one disease
OR
OR
Examples of coexistence:
• Non-specific interstitial
pneumonia (NSIP) - usual
interstitial pneumonia (UIP)
• Smoking related interstitial
diseases – RB-ILD / NSIP / Langerhan’s /
emphysema
2
1
Possible / probable
transformations:
• AIP → NSIP
• OP → NSIP / UIP?
• DIP → NSIP
• RBILD → emphysema?
• Normal → fibrosis / emphysema (aging)
• AIP – acute interstitial pneumonia
• OP – organizing pneumonia
• NSIP – non-specific interstitial pneumonia
Clearly separated in the ATS/ERS classification
Defining features of Acute
Interstitial Pneumonia (AIP) • Clinical: fulminant
• Pathology: weeping lung (DAD)
• Imaging: whiteout
Defining features of
Organizing Pneumonia (OP) • Clinical: ~non-bacterial pneumonia
• Pathology: loose granulation tissue
• Imaging: multifocal consolidation
Defining features of Non-
specific Interstitial Pneumonia
(NSIP) • Clinical: chronic indolent
• Pathology: uniform fibrosis
• Imaging: ground glass + distortion
So, AIP, OP and NSIP are very
different entities…
Strands of evidence suggesting overlap
between in situations in which AIP/NSIP/OP
occur:
• Dilated airways (irreversible) in gr. glass of ARDS
(Howling et al 1998)
• Original description of NSIP; some cases = ARDS
survivors (Katzenstein et al 1994)
• Variable behaviour of patients with polymyositis
associated lung disease (Tazelaar et al 1990)
• Accelerated phase of UIP/NSIP→AIP
(Colby 2000)
• HRCT descriptions of NSIP with consolidation
(OP) (Park et al 1998)
2000 2005 2003
Chest 2003;124:1185
• Value
– Some IIPs have diagnostic HRCT appearances
– Alternative diagnoses + complications
– Increased understanding of evolution
• Limitations
– NSIP masquerading as UIP
– Clinical significance of limited disease
– Experience / observer variation issues
HRCT and the Idiopathic Interstitial Pneumonias
Lung Cysts
Differential Diagnosis
Pulmonary fibrosis (Honeycombing)
Lymphangliomyomatosis
Langerhans cell histiocytosis
Lymphocytic Interstitial Pneumonia (LIP)
Rough Reticular Fine Reticular
Traction
Bronchiectasis
and
Interface
sign
Honey
combing
UIP UIP or NSIP
Usual Interstitial Pneumonia
UIP
HRCT Findings
Reticular opacities, thickened intra- and
interlobular septa
Irregular interfaces
Honey combing and parenchymal distorsion
Ground glass opacities (never prominent)
Basal and subpleural predominance
Basal and subpleural
distribution
UIP
The Many ‘HRCT Faces’ of NSIP
Honeycombing not a
prominent feature
!!!!
Lymphangioleiomyomatosis
(LAM)
HRCT Morphology
Thin-walled cysts (2mm - 5cm)
Uniform in size / rarely confluent
Homogeneous distribution
Chylous pleural effusion
Lymphadenopathy
in young women
Lymphangioleiomyomatosis
(LAM)
Tuberous Sclerosis (young man)
Langerhans Cell Histiocytosis
HRCT Findings
Small peribronchiolar nodules (1-5mm)
Thin-walled cysts (< 1cm),
Bizarre and confluent
Ground glass opacities
Late signs: irreversible / parenchymal fibrosis Honey comb lung, septal thickening,
bronchiectasis
1 year later
Peribronchiolar Nodules Cavitating nodules and cysts
Langerhans Cell Histiocytosis
Langerhans Cell Histiocytosis
Langerhans Cell Histiozytosis
Key Features
Upper lobe predominance
Combination of cysts and noduli
Characteristic stages
Increased Lung volume
Sparing of costophrenic angle
S
M
O
K
I
N
G
Langerhans Cell Histiocytosis
Langerhans Cell Histiocytosis
Differential Diagnosis
Only small nodules Sarcoidosis, Silicosis
Only cysts idiopathic Fibrosis
LAM
Destructive emphysema
A professional diver.............
.......after cessation of smoking
Benign lymphoproliferative
disorder Diffuse interstitial infiltration of
mononuclear cells
Not limited to the air ways as
in follicular Bronchiolitis
LIP = Lymphocytic Interstitial
Pneumonia
Sjögren: LIP
LIP = Lymphocytic Interstitial
Pneumonia
Rarely idiopathic
In association with: Sjögren‟s syndrome
Immune deficiency syndromes, AIDS
Primary biliary cirrhosis
Multicentric Castlemean‟s disease
Sjoegren disease
Dry eye and dry mouth
Fibrosis, bronchitis and bronchiolitis
LIP
Overlap
Sarcoid, DM/PM, MXCT
SLE, RA (pleural effusion)
Up to 40 x increased risk for lymphoma (mediastinal
adenopathy) and
2 x times increased risk for neoplasma
Young woman Dry mouth Smoker
LAM LIP Histiocytosis
Emphysema Fibrosis (UIP)
Wegener„s disease
Rheumatoid Arthritis
Outline
Typical HRCT patterns of lung diseases
with cysts
Mosaic pattern and its differential
Emphysema
Atypical HRCT patterns
Quiz
Where is the pathology ???????
in the areas with increased density meaning there is ground glass
in the areas with decreased density meaning there is air trapping
Pathology in black areas
Airtrapping: Airway
Disease
Bronchiolitis obliterans (constrictive bronchiolitis) idiopathic, connective tissue diseases, drug reaction,
after transplantation, after infection
Hypersensitivity pneumonitis granulomatous inflammation of bronchiolar wall
Sarcoidosis granulomatous inflammation of bronchiolar wall
Asthma / Bronchiectasis / Airway diseases
Airway Disease
what you see……
In inspiration sharply demarcated areas of seemingly increased
density (normal) and decreased density
demarcation by interlobular septa
In expiration „black‟ areas remain in volume and density
„white‟ areas decrease in volume and increase in
density
INCREASE IN CONTRAST
DIFFERENCES
AIRTRAPPING
Bronchiolitis
obliterans
Early Sarcoidosis
Chronic EAA
Hypersensitivity pneumonitis
Extr. Allerg. Alveolitis (EAA) HRCT
Morphology
chronic: fibrosis
Intra- / interlobular septal thickening
Irregular interfaces
Traction bronchiectasis
acute - subacute
acinar (centrilobular) unsharp densities
ground glass (patchy - diffuse)
Pathology in white Areas
Alveolitis / Pneumonitis
Ground glass desquamative intertitial pneumoinia (DIP)
nonspecific interstitial pneumonia (NSIP)
organizing pneumonia
In expiration both areas (white and black) decrease in
volume and increase in density
DECREASE IN CONTRAST
DIFFERENCES
DI
P
Cellular
NSIP
Mosaic Perfusion
Chronic pulmonary embolism
LOOK FOR
Pulmonary hypertension
idiopathic, cardiac disease, pulmonary
disease
CTEPH =
Chronic thrombembolic
pulmonary hypertension
HRCT: Radiographic Pattern
Radiographic Patterns in ILD Pleural Involvement
Lymphangitic Carcinomatosis
LAM
Drug Induced
Radiation Pneumonitis
Asbestosis
Effusion
Thickening
Plaques
Mesothelioma
Collagen vascular disease
Kerley B lines
Chronic LV failure
Lymphangitic CA
Lymphoma
LAM
Veno-occlusive disease
Acute Eosinophilic Pneumonia
Adenopathy
Sarcoidosis
Lymphoma
Lymphangitic CA
LIP
Amyloidosis
Berylliosis
Silicosis
Probability of Histologic Diagnosis of Diffuse Diseases
Surgical
Biopsy
1. Granulomatous diseases
2. Malignant tumors/lymphangitic
3. DAD (any cause)
4. Certain infections
5. Alveolar proteinosis
6. Eosinophilic pneumonia
7. Vasculitis
8. Amyloidosis
9. EG/HX/PLCH
10. LAM
11. RB/RBILD/DIP
12. UIP/NSIP/LIP COP
13. Small airways disease
14. PHT and PVOD
Often
Sometimes
Never
Transbronchial
Biopsy
Courtesy of Kevin O. Leslie, MD.
Practical Approach to
Interstitial Lung Diseases
Patterns of Interstitial Lung Disease
Linear Pattern A linear pattern is seen when there is
thickening of the interlobular septa,
producing Kerley lines.
Kerley B lines
Kerley A lines
The interlobular septa contain
pulmonary veins and lymphatics.
The most common cause of interlobular
septal thickening, producing Kerley A
and B lines, is pulmonary edema, as a
result of pulmonary venous
hypertension and distension of the
lymphatics. Kerley B lines
Kerley A lines
DD of Kerly Lines:
Pulmonary edema is the most common cause
Mitral stenosis
Lymphangitic carcinomatosis
Malignant lymphoma
Congenital lymphangiectasia
Idiopathic pulmonary fibrosis
Pneumoconiosis
Sarcoidosis
b. Reticular Pattern A reticular pattern results from the summation or
superimposition of irregular linear opacities.
The term reticular is defined as meshed, or in the
form of a network. Reticular opacities can be
described as fine, medium, or coarse, as the width of
the opacities increases.
A classic reticular pattern is seen with pulmonary fibrosis, in
which multiple curvilinear opacities form small cystic
spaces along the pleural margins and lung bases
(honeycomb lung)
This 50-year-old man presented with end-stage lung fibrosis
PA chest radiograph shows medium to coarse reticular
B: CT scan shows multiple small cysts (honeycombing) involving
predominantly the subpleural peripheral regions of lung. Traction
bronchiectasis, another sign of end-stage lung fibrosis.
c. Nodular pattern A nodular pattern consists of multiple round opacities,
generally ranging in diameter from 1 mm to 1 cm
Nodular opacities may be described as miliary (1 to 2 mm,
the size of millet seeds), small, medium, or large, as the
diameter of the opacities increases
A nodular pattern, especially with predominant distribution,
suggests a specific differential diagnosis
Disseminated histoplasmosis and nodular ILD.
CT scan shows multiple bilateral round circumscribed
pulmonary nodules.
Hematogenous metastases and nodular ILD. This 45-year-
old woman presented with metastatic gastric carcinoma.
The PA chest radiograph shows a diffuse pattern of
nodules, 6 to 10 mm in diameter.
Differential diagnosis of a nodular
pattern of interstitial lung disease
SHRIMP Sarcoidosis
Histiocytosis (Langerhan cell
histiocytosis)
Hypersensitivity pneumonitis
Rheumatoid nodules
Infection (mycobacterial, fungal, viral)
Metastases, Miliary TB
Microlithiasis, alveolar
Pneumoconioses (silicosis, coal
worker's, berylliosis)
d. Reticulonodular pattern A reticulonodular pattern results from a
combination of reticular and nodular opacities.
This pattern is often difficult to distinguish from a purely reticular or nodular pattern, and in such a case a differential diagnosis should be developed based on the predominant pattern.
If there is no predominant pattern, causes of both nodular and reticular patterns should be considered.
How To Approach
a Practical
Diagnosis?
An acute appearance suggests pulmonary edema, acute milliary TB, or acute interstitial neumonia,acute esinophillic pneumonia
Rule no. 1
Disseminated histoplasmosis and reticulonodular ILD.
A: PA chest radiograph, close-up of right upper lung, shows reticulonodular
ILD.
B: CT scan shows multiple circumscribed round pulmonary nodules, 2 to 3
mm in diameter.
Reticulonodular lower lung predominant
distribution with decreased lung volumes
suggests: (APC)
1. Asbestosis
2. Aspiration (chronic)
3. Pulmonary fibrosis (idiopathic)
4.Collagen vascular disease
Rule no. 2
Asbestos-related
pleural disease and
asbestosis
Pulmonary fibrosis and rheumatoid arthritis.
Systemic sclerosis. A: PA chest radiograph shows a bibasilar and subpleural distribution of fine
reticular ILD. The presence of a dilated esophagus (arrows) provides a clue
to the correct diagnosis.
B: CT scan shows peripheral ILD and a dilated esophagus (arrow).
A middle or upper lung predominant distribution
suggests: (Mycobacterium Settle Superiorly in
Lung)
1. Mycobacterial or fungal disease
2. Silicosis
3. Sarcoidosis
4. Langerhans Cell Histiocytosis
Rule no. 3
Complicated silicosis. PA chest radiograph shows multiple
nodules involving the upper and middle lungs, with coalescence
of nodules in the left upper lobe resulting in early progressive
massive fibrosis
Sarcoidosis. CT scan shows nodular thickening of the bronchovascular
bundles (solid arrow) and subpleural nodules (dashed arrow), illustrating the
typical perilymphatic distribution of sarcoidosis.
Langerhan cell histiocytosis.
This 50-year-old man had a
30 pack-year history of
cigarette smoking.
A: PA chest radiograph
shows hyperinflation of the
lungs and fine bilateral
reticular ILD.
B: CT scan shows multiple
cysts (solid arrow) and
nodules (dashed arrow).
Associated lymphadenopathy suggests :
1.Sarcoidosis-Berryliosis
2.neoplasm (lymphangitic carcinomatosis,
lymphoma, metastases)
3. infection (viral, mycobacterial, or fungal)
4. silicosis
Rule no. 4
Simple silicosis.
A: CT scan with lung windowing shows numerous
circumscribed pulmonary nodules, 2 to 3 mm in diameter
(arrows).
B: CT scan with mediastinal windowing shows densely
calcified hilar (solid arrows) and subcarinal (dashed arrow)
nodes.
Associated pleural thickening and/or
calcification suggest asbestosis.
Rule no. 5
Associated pleural effusion suggests :
1.pulmonary edema
2.lymphangitic carcinomatosis
3.lymphoma
4.collagen vascular disease
5.LAM
Rule no. 6
Cardiogenic pulmonary edema.
PA chest radiograph shows enlargement of the cardiac
silhouette, bilateral ILD, enlargement of the azygos vein
(solid arrow), and peribronchial cuffing (dashed arrow).
Lymphangitic carcinomatosis. This 53-year-old man
presented with chronic obstructive pulmonary disease and
large-cell bronchogenic carcinoma of the right lung.
CT scan shows unilateral nodular thickening (arrows) and a
malignant right pleural effusion.
Associated pneumothorax suggests
lymphangioleiomyomatosis or LCH.
Rule no. 7
Lymphangioleiomyomatosis
(LAM).
A: PA chest radiograph shows a
right basilar pneumothorax and
two right pleural drainage
catheters. The lung volumes are
increased, which is
characteristic of LAM, and there
is diffuse reticular ILD.
B: CT scan shows bilateral thin-
walled cysts and a loculated
right pneumothorax (P).
Approach to the ILD Patient
M artinez F , F laherty K . Available a t: h ttp ://www.chestnet.org/ed ucation/online/pccu/vol18/lessons03_04/lesson03.php.
Patient w ith S uspected
ILD
H x, PE , C XR , PFT , Labs
STO P
H R C T
H x and H R C T
consistent
w ith IPF
H x and H R C T
D x of o ther
ILD
Suspected
other ILD
A typical
c lin ical o r C T
features of IPF
STO P STO P
STO P
VA TS
U IP N on IIPLIPO PD A DD IPN SIP R B ILD
Yes
N o
Yes
N o
D x likely by
bronch?
Is bronch
diagnostic?
D x likely by
bronch?
Is bronch
diagnostic?
Yes
Yes
N o
