ipf or non ipf interstitial lung diseases

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