The importance of The importance of radiological radiological evaluation in the evaluation in the discrimination discrimination between UIP and NSIPbetween UIP and NSIP

Dr. Figen Başaran DemirkazıkDr. Figen Başaran Demirkazık

Hacettepe ÜHacettepe Üniniversity Department of versity Department of RRadadiologyiology

HRCT Indications

Chronic disease: To detect lung diseases in patients who have To detect lung diseases in patients who have

normal or questionable radiographic normal or questionable radiographic abnormalities, who have symptoms or abnormalities, who have symptoms or pulmonary function findings suggestive of pulmonary function findings suggestive of diffuse lung disease.diffuse lung disease.

To analyse and limit the differential diagnosis To analyse and limit the differential diagnosis of parenchymal lung diseases (sarcoidosis, of parenchymal lung diseases (sarcoidosis, lymphangitic carcinomatosis, histiocytosis X, lymphangitic carcinomatosis, histiocytosis X, interstitial fibrozis)interstitial fibrozis)

HRCT Indications

Chronic disease: To assess disease activity and

response to treatment

As a guide for the need or optimal site and type of lung biopsy

HRCT Indications

Acute disese: To detect lung diseases in patients who To detect lung diseases in patients who

have symptoms of acute lung disease have symptoms of acute lung disease and normal or nondiagnostic chest and normal or nondiagnostic chest radiographs, particularly in radiographs, particularly in immunocompromised patients. immunocompromised patients.

acute- chronic dispnea, chest pain, acute- chronic dispnea, chest pain, fever of unknown origin, abnormal fever of unknown origin, abnormal pulmonary functions, fever after BMT or pulmonary functions, fever after BMT or organ transplantation, infection in AIDS organ transplantation, infection in AIDS patientspatients

1-1.5 mm8.5-9 mm

HRCT

Slice thickness 5 mm Slice thickness 1 mm

Soft tissue filter Bone filter

Kesit kalınlığı 1 mm Kesit kalınlığı 1 mm

ATS, ERS International Multidisciplinary Consensus Classification of the Idiopathic InterstitialPneumonias. Am J Respir Crit Care Med 2002;165:277–304.

USUAL INTERSTITIAL USUAL INTERSTITIAL PNEUMONIA/ IPF-PNEUMONIA/ IPF- clinical clinical featuresfeatures

• Patients Patients >> 50 years old, a median survival time ranging 50 years old, a median survival time ranging from 2 to 4 years,from 2 to 4 years,

• Progressive worsening dyspnea and nonproductive cough Progressive worsening dyspnea and nonproductive cough subtle onset of symptoms subtle onset of symptoms

• Slightly more cases in men than womenSlightly more cases in men than women

• A history of cigarette smoking seems to be a risk factor A history of cigarette smoking seems to be a risk factor

• Do not respond to highdose corticosteroid therapy; Do not respond to highdose corticosteroid therapy; A combination therapy of cytotoxic drugs and A combination therapy of cytotoxic drugs and corticosteroids seems to be efficacious for acute corticosteroids seems to be efficacious for acute exacerbations of IPF. exacerbations of IPF.

USUAL INTERSTITIAL USUAL INTERSTITIAL PNEUMONIA-PNEUMONIA- histologic featureshistologic features

• The histologic hallmark of UIP is the presence of scattered The histologic hallmark of UIP is the presence of scattered fibroblastic foci fibroblastic foci

• Typically, involvement is heterogeneous and areas of Typically, involvement is heterogeneous and areas of normal normal lung lung alternate with interstitial inflammation alternate with interstitial inflammation and honeycombing and honeycombing

• Owing to the patchy lung involvement, histologic Owing to the patchy lung involvement, histologic evaluation of evaluation of multiple biopsy specimens from one patient multiple biopsy specimens from one patient may reveal may reveal discordant histologic patterns. discordant histologic patterns.

• Biopsy samples from more than one lobe should beBiopsy samples from more than one lobe should beobtained in any patient with suspected IIPobtained in any patient with suspected IIP

• High resolution CT should serve as a guiding toolHigh resolution CT should serve as a guiding toolfor determining the appropriate anatomic locationfor determining the appropriate anatomic location

USUAL INTERSTITIALUSUAL INTERSTITIALPNEUMONIA/ IPF-PNEUMONIA/ IPF- imaging imaging featuresfeatures

Chest X-ray:Chest X-ray:

• May be normal in early diseaseMay be normal in early disease

• In advanced disease, it shows decreased lung In advanced disease, it shows decreased lung volumes and subpleural reticular opacities that volumes and subpleural reticular opacities that increase from the apex to the bases of the increase from the apex to the bases of the lungslungs

USUAL INTERSTITIALUSUAL INTERSTITIALPNEUMONIA/ IPF-PNEUMONIA/ IPF- imaging imaging featuresfeatures

HRCT:HRCT:A Trio of signs: A Trio of signs:

• Apicobasal gradientApicobasal gradient• Subpleural reticular opacitiesSubpleural reticular opacities• Macrocystic honeycombing combined with traction Macrocystic honeycombing combined with traction

bronchiectasisbronchiectasis

• Ground- glass opacities are limitedGround- glass opacities are limited

• Histologic confirmation should be obtained in patients with Histologic confirmation should be obtained in patients with atypical imaging findings, such as extensive ground-glass atypical imaging findings, such as extensive ground-glass opacities, nodules, consolidation, or a predominantly opacities, nodules, consolidation, or a predominantly peribronchovascular distributionperibronchovascular distribution

UIP

64 y, M 12 months later

67 y, M

IPF

Acute Exacerbations of IPFAcute Exacerbations of IPF

Criteria of acute exacerbations Criteria of acute exacerbations

1) Acute worsening of dyspnea within 1 month of presentation1) Acute worsening of dyspnea within 1 month of presentation

2) New pulmonary infiltrates seen on CXRs or CT scans2) New pulmonary infiltrates seen on CXRs or CT scans

3) Deterioration in pulmonary function measurements or gas 3) Deterioration in pulmonary function measurements or gas exchangeexchange

4) Absence of an identifiable cause, including infections or 4) Absence of an identifiable cause, including infections or cardiovascular disease.cardiovascular disease.

Noth I, CHEST 2007; 132:637–650

Acute Exacerbations of IPFAcute Exacerbations of IPF

HRCT:HRCT:new diffuse, multifocal, or peripheral new diffuse, multifocal, or peripheral ground-glass ground-glass opacities superimposed on subpleural reticular and honeycombing densities.

Pathology: Pathology: acute alveolar injury with or without acute alveolar injury with or without hyaline membrane formation.hyaline membrane formation.

Noth I, CHEST 2007; 132:637–650

Clinical conditions associated with UIP pattern• Idiopathic pulmonary

fibrosis/cryptogenic fibrosing alveolitis

• Collagen vascular disease• Drug toxicity• Chronic hypersensitivity

pneumonitis• Asbestosis

RA

RA

NONSPECIFIC INTERSTITIAL NONSPECIFIC INTERSTITIAL PNEUMONIA:PNEUMONIA: clinical featuresclinical features

• 40- 50 years old, F=M40- 50 years old, F=M

• Symptoms are similar to those of IPF but usually milder.Symptoms are similar to those of IPF but usually milder.

• Gradually worsening dyspnea over several months, with Gradually worsening dyspnea over several months, with fatigue and weight loss.fatigue and weight loss.

• Cigarette smoking is not a risk factor Cigarette smoking is not a risk factor

• Majority of patients stabilize or improve with Majority of patients stabilize or improve with corticosteroids in combination with cytotoxic drugs corticosteroids in combination with cytotoxic drugs (cyclophosphamide, cyclosporin)(cyclophosphamide, cyclosporin)

NONSPECIFIC INTERSTITIAL NONSPECIFIC INTERSTITIAL PNEUMONIA:PNEUMONIA: histolojic featureshistolojic features

• Temporally and spatially homogeneous lung Temporally and spatially homogeneous lung involvementinvolvement

• Cellular subtype: Cellular subtype: The thickening of alveolar septa is The thickening of alveolar septa is primarily caused by inflammatory cellsprimarily caused by inflammatory cells

• Fibrosing subtype: Fibrosing subtype: Interstitial fibrosis is seen in Interstitial fibrosis is seen in addition to mild inflammationaddition to mild inflammation

• Cellular NSIP is less common than fibrosing NSIP but Cellular NSIP is less common than fibrosing NSIP but shows a better response to corticosteroids and carries shows a better response to corticosteroids and carries a substantially better prognosisa substantially better prognosis

Does NSIP evolve into UIP?

The initial injury in UIP could itself cause secondary inflammation and fibrosis that resemble NSIP. No reports have documented the progression of NSIP to UIP.

NONSPECIFIC NONSPECIFIC INTERSTITIALINTERSTITIAL PNEUMONIA:PNEUMONIA: imaging featuresimaging features

Chest X-ray:Chest X-ray:

In early NSIP: In early NSIP: the chest radiograph is normal.the chest radiograph is normal.

In advanced NSIP: In advanced NSIP: bilateral pulmonary infiltrates bilateral pulmonary infiltrates

The lower lung lobes are more frequently The lower lung lobes are more frequently involved, but an obvious apicobasal gradient, as involved, but an obvious apicobasal gradient, as seen in UIP, is usually missing.seen in UIP, is usually missing.

NONSPECIFIC INTERSTITIAL NONSPECIFIC INTERSTITIAL PNEUMONIA:PNEUMONIA: imaging featuresimaging features

HRCT:HRCT:Subpleural and rather symmetric distribution.Subpleural and rather symmetric distribution.Patchy ground-glass opacities are combined with irregular Patchy ground-glass opacities are combined with irregular

linear or reticular opacitielinear or reticular opacitiess

In advanced disease:In advanced disease: traction bronchiectasis and traction bronchiectasis and consolidationconsolidation

Ground-glass opacities remain the most obvious HRCT signGround-glass opacities remain the most obvious HRCT signSubpleural cysts are smaller and limited in extent than those Subpleural cysts are smaller and limited in extent than those

of UIP.of UIP.Microcystic honeycombing: Microcystic honeycombing: NSIPNSIPMacrocystic honeycombing: Macrocystic honeycombing: UIPUIP

Fibrotic NSIP: Fibrotic NSIP: honeycombing, traction bronchiectasis and honeycombing, traction bronchiectasis and intralobular reticular opacities.intralobular reticular opacities.

Fibrosing NSIP

Cellular NSIP

60 y , F

53 y, M

Pathology:NSIP

NSIPPathology:NSIP

Clinical conditions associated with NSIP pattern

• Idiopathic NSIP• Collagen vascular disease• Hypersensitivity pneumonitis• Drug-induced pneumonitis• Infection• Immunodeficiency including HIV

infection

Drug reaction

Skleroderma

Asbestosis

UIP(n = 44) NSIP (n = 50)

Craniocaudal planeUpper zone predominance 2 (4.5) 1 (2)Middle zone predominance 1 (2) 1 (2)Lower zone predominance 37 (85) 45 (90)Equal in all zones 4 (9) 3 (6) Axial planePeripheral predominance 42 (95) 37 (74)Central Predominance 1 (2) 0Diffuse distribution 1 (2) 13 (26) HomogeneityPatchy distribution 27 (61) 15 (30)Confluent distribution 17 (39) 35 (70) Ancillary findingsMediastinal adenopathy 20 (45) 27 (54)Pulmonary artery enlargement 8 (18) 14 (28).

Eliot TL, J Comput Assist Tomogr 2005;29:339

The presence of honeycombing as a predominant feature had a specificity of 96%, sensitivity of 41%, positive predictive value of 90%, and negative predictive value of 64% for UIP (P, 0.001).

The pattern of predominant ground-glass attenuation + reticular opacity with minimal to no honeycombing had a sensitivity of %96 and a specificity of 41% for the diagnosis of NSIP. The absence of honeycombing as a predominant feature has a high negative predictive value for NSIP (90%).

Eliot TL, J Comput Assist Tomogr 2005;29:339

NSIP vs UIPNSIP vs UIP

The key CT features in the diagnosis of NSIP over The key CT features in the diagnosis of NSIP over UIP:UIP:

• Homogeneous lung involvement Homogeneous lung involvement • Without an obvious apicobasal gradientWithout an obvious apicobasal gradient• Extensive ground-glass abnormalities,Extensive ground-glass abnormalities,• Finer reticular patternFiner reticular pattern• Absence of honeycombingAbsence of honeycombing• Relative subpleural sparing*Relative subpleural sparing*

**Silva CI, Radiology. 2008; 246: 288Silva CI, Radiology. 2008; 246: 288

NSIP vs UIPNSIP vs UIPFollow-up:Follow-up:

In UIP: In UIP: progression of ground-glass attenuation to progression of ground-glass attenuation to honeycombing is common and indicates irreversible honeycombing is common and indicates irreversible fibrosis fibrosis

In NSIP: In NSIP: ground-glass opacities usually do not progress ground-glass opacities usually do not progress to areas of honeycombing, even if there is to areas of honeycombing, even if there is associated bronchiectasisassociated bronchiectasis

At follow-up CT, 28% of patients with initial CT At follow-up CT, 28% of patients with initial CT findings suggestive of NSIP progressed to findings findings suggestive of NSIP progressed to findings suggestive of IPF.suggestive of IPF.**

**Silva CI, Radiology 2008; 247:251Silva CI, Radiology 2008; 247:251

PrognosisPrognosisMedian survival time: Median survival time: NSIP:12 years NSIP:12 years

UIP: 2.8 years UIP: 2.8 years

5-year survival rates : 5-year survival rates : Cellular NSIP: 100% Cellular NSIP: 100% Fibrotic NSIP: 90%Fibrotic NSIP: 90% UIP : 43%UIP : 43%

10-year survival rates: 10-year survival rates: Cellular NSIP: 100% Cellular NSIP: 100% Fibrotic NSIP: 35%Fibrotic NSIP: 35% UIP : 15%UIP : 15%

Cellular NSIP > Fibrotic NSIP > UIP/IPF.Cellular NSIP > Fibrotic NSIP > UIP/IPF.

Leslie KO, CHEST 2005; 128:513S

Sens %Sens %Spec %Spec %

IPF- clinical diag.IPF- clinical diag. 62 62 97 97IPF- radiologic diag.IPF- radiologic diag. 78.5 78.5 90 90

Non IPF- ILD : clinical diag.Non IPF- ILD : clinical diag. 88.8 88.8 40 40Non IPF- ILD: radiologic diag.Non IPF- ILD: radiologic diag. 59 59 40 40

Raghu G, CHEST 1999; Raghu G, CHEST 1999; 116:1168–1174116:1168–1174

Correct Diagnoses of HRCTCorrect Diagnoses of HRCTAccording to DiseaseAccording to Disease

Correct DiagnosisCorrect Diagnosis Correct DiagnosisCorrect DiagnosisWith High LevelWith High Levelof Confidenceof Confidence

NSIP (n=36) NSIP (n=36) 79.279.2 65.3 65.3UIP (n=11) UIP (n=11) 100 100 90.9 90.9COP (n=8) COP (n=8) 75.0 75.0 43.8 43.8AIP (n=10) AIP (n=10) 75.0 75.0 40.0 40.0DIP or RB-ILD DIP or RB-ILD 35.7 35.7 32.1 32.1LIP (n = 11) LIP (n = 11) 95.595.5 81.8 81.8

Total (n = 90) Total (n = 90) 76.1 76.1 60.6 60.6

Tsubamoto M, J Comput Assist Tomogr 2005;29:793

ATS-ERS Criteria for Diagnosis of IPF in ATS-ERS Criteria for Diagnosis of IPF in the Absence of Surgical Lung Biopsythe Absence of Surgical Lung Biopsy

Major criteriaMajor criteriaExclusion of other known causes of interstitial lung disease Exclusion of other known causes of interstitial lung disease

(eg, toxic effects of certain drugs, environmental exposures,(eg, toxic effects of certain drugs, environmental exposures, and and connective tissue diseases)connective tissue diseases)

Abnormal results of pulmonary function studies, including Abnormal results of pulmonary function studies, including evidence of restriction (reduced vital capacity, oftenevidence of restriction (reduced vital capacity, often with an with an increased FEV1/FVC ratio) and impaired gas exchange (increased increased FEV1/FVC ratio) and impaired gas exchange (increased PP(A-(A-aa))oo22 decreased Pao2 with decreased Pao2 with rest or exercise, or decreased Dlco)rest or exercise, or decreased Dlco)

Bibasilar reticular abnormalities with minimal ground-glass Bibasilar reticular abnormalities with minimal ground-glass opacities at high-resolution CTopacities at high-resolution CT

Transbronchial lung biopsy or bronchoalveolar lavage Transbronchial lung biopsy or bronchoalveolar lavage shows no features to support an alternative diagnosisshows no features to support an alternative diagnosis

Minor criteriaMinor criteriaAgeAge > > 50 y 50 yInsidious onset of otherwise unexplained dyspnea on exertionInsidious onset of otherwise unexplained dyspnea on exertionDuration of illnessDuration of illness > > 3 mo 3 moBibasilar inspiratory crackles (dry or “Velcro” type)Bibasilar inspiratory crackles (dry or “Velcro” type)

ATS, ERS International Multidisciplinary Consensus Classification of the Idiopathic InterstitialPneumonias. Am J Respir Crit Care Med 2002;165:277–304.

Potential Limitations of Clinical Criteria Potential Limitations of Clinical Criteria for thefor theDiagnosis of IPF/CFADiagnosis of IPF/CFA

HRCTHRCT % % ATS % ATS % Sensitivity Sensitivity 71 71 71 71 Specificity Specificity 6767 7575PPVPPV 7171 7777NPVNPV 6767 6969Accuracy Accuracy 6969 7373

Peckham RM, Respiration 2004;71:165

Should You Biopsy Every Patient?Should You Biopsy Every Patient?

• Given the potential risks and a better definition ofGiven the potential risks and a better definition ofthe diagnostic accuracy of a HRCT scan diagnosis,the diagnostic accuracy of a HRCT scan diagnosis,SLB is not required in all patients with suspectedSLB is not required in all patients with suspectedIPF. IPF.

• It is becoming increasingly accepted that aIt is becoming increasingly accepted that ahighly suggestive clinical presentation, including highly suggestive clinical presentation, including typicaltypicalHRCT scan findings, can be used in the absenceHRCT scan findings, can be used in the absenceof a lung biopsy specimen to make a likely of a lung biopsy specimen to make a likely diagnosis of IPFdiagnosis of IPF

Noth I, CHEST 2007; 132:637

• As a general rule, a suspected diagnosis As a general rule, a suspected diagnosis of NSIP will always require a surgical of NSIP will always require a surgical biopsy, whereas a confident diagnosis of biopsy, whereas a confident diagnosis of IPF without a biopsy is usually correctIPF without a biopsy is usually correct..

du Bois R,Thorax 2007;62:1008

What is the purpose of performing a What is the purpose of performing a surgical biopsy? surgical biopsy?

1. Knowing at presentation that an individual has NSIP and not UIP 1. Knowing at presentation that an individual has NSIP and not UIP allows the clinician to convey a more optimistic prognosis;allows the clinician to convey a more optimistic prognosis;

2. A short course of higher dose corticosteroids may have a 2. A short course of higher dose corticosteroids may have a significantly better efficacy/side effect profile in NSIP than in UIPsignificantly better efficacy/side effect profile in NSIP than in UIP

3. Even with alternative (immunosuppression) first-line treatment3. Even with alternative (immunosuppression) first-line treatmentapproaches, the balance of likely good versus adverse effects can approaches, the balance of likely good versus adverse effects can be articulated with more precision to an individual patient rather be articulated with more precision to an individual patient rather than than quoting average survival and side effect data. quoting average survival and side effect data.

4. Trials of new treatment are being undertaken on individuals 4. Trials of new treatment are being undertaken on individuals with with well defined disease in order to maximise the likely response to well defined disease in order to maximise the likely response to thethe novel agentnovel agent..

du Bois R,Thorax 2007;62:1008

IPF

Pathology:UIP

Pathology:UIP 31 y

Pathology:UIP

52 years old, M He presented with left back and

left flank pain. There was no finding on physical

examination.

Pathology: Homogeneous fibrozis with

intraalveolar macrophage aggregates

NSIP? DIP?

• 38 years old, male38 years old, male• Cough in cold weatherCough in cold weather• Dispnea for 13 monthsDispnea for 13 months

3259230 mustafakıratDiagnosis?

Pathology: UIP

UIPUIP NSIPNSIP

HRCT FeaturesHRCT Features

Reticular opacities- Reticular opacities-

interlobular septal interlobular septal

thickeningthickening

Macrocystic honeycombingMacrocystic honeycombing,,

Traction bronchiectasis,Traction bronchiectasis,

Architectural distortion,Architectural distortion,

Focal ground-glass opacityFocal ground-glass opacity

HRCT Features HRCT Features

Ground-glass opacitiesGround-glass opacities

SSymmetric irregularymmetric irregular l linear inear

oror rreticular opacities eticular opacities

CConsolidationonsolidation

MiMicrocysticcrocystic honeycombinghoneycombing

Zeus Tapınağı- Aizonia- Kütahya