Classification of idiopathic interstitial pneumonias: what is new since 2002?

MINI-SYMPOSIUM: PATHOLOGY OF NON-NEOPLASTIC LUNG DISEASE

Classification of idiopathicinterstitial pneumonias: whatis new since 2002?Mary Beth Beasley

AbstractSince the introduction of the 2002 ATS/ERS consensus classification of inter-

stitial lung disease, the body of literature has greatly expanded. As such, an

updated classification is in the final review stages at the time of this writing.

In addition, the clinical diagnosis of idiopathic pulmonary fibrosis has been

refined, incorporating multidisciplinary guidelines. Similarly, the entity of

clinically idiopathic non-specific interstitial pneumonia has been better

defined. The issue of smoking-related interstitial fibrosis, while in some

ways controversial, has also been better established. The aim of this article

is to review updates in the major categories of interstitial lung disease since

2002 and discuss the concept of smoking-related interstitial fibrosis.

Keywords consensus classification; idiopathic pulmonary fibrosis; non-

specific interstitial pneumonia; smoking-related interstitial fibrosis; usual

interstitial pneumonia

Introduction

In 2002, an international consensus classification for the diag-

nosis of idiopathic interstitial pneumonias was published as a

joint statement from the American Thoracic Society (ATS) and

the European Respiratory Society (ERS).1 This statement

emphasized a multidisciplinary approach to interstitial lung

disease (ILD) and proposed a uniform set of definitions and

criteria for the diagnosis of idiopathic interstitial pneumonias

(IIPs). The 2002 consensus statement defined seven histologic

patterns of disease and the corresponding clinical classification of

idiopathic disease. The 2002 classification is presented in Table

1. It was also recognized that some patients with clinical IIP

have disease patterns which do not meet criteria for any of the

main classifications and the category of “unclassified” was also

included to encompass this group.1

In the subsequent 10 years since the publication of the ATS/ERS

classification, the body of knowledge of IIP’s has greatly expanded,

which has resulted in a recently proposed update of the 2002 clas-

sification, still in press at the time of thiswriting.2 Themain entities

of the 2002 classification are retained in the update. The primary

proposed changes include removal of the term “provisional” from

the clinical entity of idiopathic non-specific interstitial pneumonia

(NSIP), as this entity is now better defined. It is further proposed

that IIP’s should be divided into “major” and“rare”. In this scheme,

lymphocytic interstitial pneumonia (LIP) has been moved to the

“rare” category and pleuropulmonary fibroelastosis (PPFE) has

Mary Beth Beasley MD Associate Professor of Pathology, Mount Sinai

Medical Center, New York, USA. Conflicts of interest: none declared.

DIAGNOSTIC HISTOPATHOLOGY 19:8 267

also been introduced in this category. Other histologic patterns of

ILD such as acute fibrinous and organizing pneumonia (AFOP) and

bronchiolocentric interstitial pneumonias are formally addressed

but not included as categories of IIP at this time due to a lack of data

supportingwhether these are distinct IIPs or rare patterns related to

other IIPs.2 The updated schema is presented in Table 2. A category

of unclassifiable idiopathic interstitial pneumonias is also retained.

The aimof this article is to reviewupdates in themajor categories of

IIPs. “New” histologic patterns of PPFE, AFOP and bronchiolo-

centric interstitial pneumonias as well as molecular abnormalities/

familial ILD will be discussed in other articles in this issue.

Usual interstitial pneumonia (UIP)/Idiopathic pulmonary fibrosis

(IPF) e update on diagnostic guidelines

In 2011, an updated guideline was published for diagnosis and

management of idiopathic pulmonary fibrosis (IPF), which pro-

posed a diagnostic algorithm for correlating histologic and radio-

logic findings.3 This document again emphasizes the importance

of a multidisciplinary approach to diagnosis and introduces three

levels of certainty for interpretation of high resolution CT scan

(HRCT) e usual interstitial pneumonia (UIP), possible UIP and

inconsistent with UIP. Histologic levels of certainty were also

introduced which encompassed UIP, “probable UIP”, “possible

UIP”, and “not UIP.” The histologic criteria for UIP in this docu-

ment remain those well known to pathologists: 1) Heterogenous

fibrosis with areas of severe fibrosis associated with architectural

distortion and/or honeycomb change alternating with areas of

relatively sparedparenchyma2) Fibrosis present preferentially in a

subpleural and paraseptal distribution and 3) Evidence of “tem-

poral heterogeneity” in the formof fibroblast foci (Figures 1 and 2).

Features suggesting an alternative diagnosis, discussed subse-

quently, should be absent. In this document, “Probable UIP” is

defined as 1) Evidence ofmarked fibrosis/architectural distortion/

honeycombing 2)Absence of patchy involvement or fibroblast foci

but not both 3) Absence of features against a diagnosis of UIP

suggesting an alternate diagnosis OR 1) Honeycomb changes only;

“Possible UIP” is defined as 1) Patchy or diffuse involvement of

lung parenchyma by fibrosis without interstitial inflammation 2)

Absence of other criteria for UIP as defined in the document and 3)

Absence of features against a diagnosis of UIP. Criteria for “Not

UIP” include the presence of any of the six following features 1)

Hyaline membranes 2) Organizing pneumonia 3) granulomas 4)

Marked interstitial inflammatory cell infiltrate away from honey-

comb areas 5) Predominant airway centered changes 6) Other

features suggesting an alternative diagnosis.3

Certainty of diagnosis is then made upon the combination of

HRCT and histologic findings, and underlying etiologies need to

be excluded before a final clinical diagnosis of IPF is made. Ul-

timately, a clinical diagnosis of IPF requires 1) exclusion of other

known causes of ILD 2) the presence of a UIP pattern on HRCT in

patients not subjected to surgical lung biopsy and 3) specific

combinations of HRCT and lung biopsy patterns in patients who

have undergone surgical biopsy.3

Additional issues in the differential diagnosis of UIP

Acute exacerbation of UIP

Acute exacerbation is clinically defined as a worsening of disease

and new bilateral ground glass opacities or consolidation in the

� 2013 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.mpdhp.2013.06.009

2002 ATS/ERS classification of idiopathic interstitialpneumonias

Histologic pattern Multidisciplinary clinical classification

for idiopathic disease

Usual interstitial

pneumonia

Idiopathic pulmonary fibrosis/

cryptogenic fibrosing alveolitis

Non-specific interstitial

pneumonia

Non-specific interstitial pneumonia

(provisional)

Organizing pneumonia Cryptogenic organizing pneumonia

Diffuse alveolar damage Acute interstitial pneumonia

Respiratory bronchiolitis Respiratory bronchiolitis-interstitial

lung disease

Desquamative interstitial

pneumonia

Desquamative interstitial pneumonia

Lymphoid interstitial

pneumonia

Lymphoid interstitial pneumonia

Table 1

Figure 1 Usual interstitial pneumonia. Low power demonstrating severe

interstitial fibrosis with architectural remodeling preferentially involving

the subpleural regions adjacent to comparatively spared lung paren-

chyma. H&E, 40�.


absence of superimposed infection, cardiac failure or other cau-

ses of acute lung injury. While the clinical scenario of acute

exacerbation may be encountered in any fibrosing lung disease, it

has been most commonly reported and encountered in UIP/IPF.

Histologically, acute exacerbation is most frequently character-

ized by hyaline membranes superimposed on underlying UIP;

however, some cases may exhibit superimposed organizing

pneumonia. A pattern of frequent, large fibroblast foci has also

Proposed updated ATS/ERS idiopathic interstitialpneumonia classification

Major idiopathic interstitial pneumonias

Histologic pattern Multidisciplinary clinical

diagnosis for idiopathic disease

Usual interstitial pneumonia

(UIP)

Idiopathic pulmonary fibrosis

(IPF)

Non-specific interstitial

pneumonia (NSIP)

Idiopathic non-specific

interstitial pneumonia

Respiratory bronchiolitis (RB) Respiratory bronchiolitis-

interstitial lung disease (RB-ILD)


pneumonia (DIP)


pneumonia (DIP)

Organizing pneumonia (OP) Cryptogenic organizing

pneumonia (COP)

Diffuse alveolar damage (DAD) Acute interstitial pneumonia

(AIP)

Rare idiopathic interstitial pneumonias

Idiopathic lymphoid interstitial pneumonia

Idiopathic pleuropulmonary fibroelastosis

Rare histologic patterns

Acute fibrinous and organizing pneumonia

Bronchiolocentric patterns of interstitial pneumonias

Table 2


been described. Acute exacerbation of fibrosing lung disease is

associated with an extremely poor outcome.4,5

Hypersensitivity pneumonitis (HSP)

Chronic HSP may mimic other ILD’s both radiographically and

histologically. In the past decade both the histologic and radio-

graphic findings of HSP have been better defined. Classically,

HSP is characterized by peribronchiolar chronic inflammation

with associated giant cells and/or poorly formed granulomas;

however, these features are typically found in cases of clinically

subacute disease and the histologic features of chronic HSP were

not well documented. Churg et al., examined a series of patients

with well documented HSP clinically and described the histology

of chronic HSP as consisting of patchy subpleural fibrosis with

temporal heterogeneity resembling UIP with or without “NSIP-

like areas” and peribronchiolar fibrosis. Some cases showed

diffuse fibrosis otherwise consistent with NSIP. All cases had

Figure 2 Usual interstitial pneumonia. Fibroblast foci in UIP are charac-

terized by loosely arranged areas of bluish-gray fibroblastic tissue as

opposed to dense collagenous fibrosis. H&E, 600�.




identifiable giant cells or poorly formed granulomas. In some

instances Schaumann bodies were the only evidence of prior

granulomatous inflammation. In some cases, features of “classic”

HSP as described above were also present.6 The take home

message is that in cases in which a diagnosis of UIP or NSIP is

being considered histologically, careful observation for a

component of peribronchiolar disease and/or granulomas should

be undertaken (Figures 3 and 4). Correlation with HRCT can be

invaluable in these cases as review may reveal clues such as

upper lobe distribution, centrilobular nodules and air trapping

which would suggest HSP over UIP or NSIP.6,7

Collagen vascular disease related ILD

Figure 4 Hypersensitivity pneumonitis. In the same case as illustrated in

Figure 3, loosely formed granulomas and giant cells containing Schau-

mann bodies are seen. H&E 600�.

Collagen vascular diseases (CVD) of all types are a frequent

cause of ILD. Although a variety of histologic patterns have been

reported in association with underlying CVD, many cases may

mimic either UIP or NSIP. While several studies have attempted

to clarify the histologic features associated with ILD related to

CVD, none have proven to be entirely pathognomonic. Histologic

features which should raise the issue of CVD include the pres-

ence of significant inflammation and, in particular, lymphoid

follicles away from areas of end stage fibrosis, presence of

pleuritis and a histologic pattern which is does not precisely fit

either UIP or NSIP. Some studies have also noted that the

quantity and size of fibroblast foci in CVD-related disease were

smaller than those of IPF however this is subjectively difficult to

ascertain in an individual case.8e12

Non-specific interstitial pneumonia (NSIP)

NSIP was originally described as a subset of ILD which was

histologically and clinically distinct from UIP. Originally catego-

rized into cellular, mixed cellular and fibrotic and fibrotic forms,

NSIP is current categorized into cellular and fibrosing subtypes

given the presence of fibrosis governs the ultimate behavior. In

2008, a multidisciplinary review and consensus statement was

published following an ATS workshop which refined diagnostic

criteria for NSIP.13 Histologically, the diagnostic criteria are

Figure 3 Hypersensitivity pneumonitis. Chronic hypersensitivity pneumo-

nitis may resemble UIP and even have occasion fibroblast foci as illus-

trated in this picture. H&E 400�.


presented in Table 3. In addition to the diffuse, temporally uni-

form fibrosis which characterizes NSIP in contrast to UIP, an

important distinction is differentiation of honeycomb fibrosis

seen in UIP from so-called “enlarged airspaces” seen in NSIP. In

UIP, honeycomb fibrosis is characterized by architectural

remodeling of the lung parenchyma and residual enlarged air-

spaces are often lined by respiratory and even squamous

epithelium. In contrast, honeycomb change is generally absent in

NSIP and rather, airspaces appear enlarged but the overall ar-

chitecture of the lung is preserved (Figures 5 and 6). NSIP differs

from UIP radiographically as well. Unlike UIP, NSIP is typically

characterized by diffuse ground glass changes as opposed to

peripheral, basilar fibrosis with honeycomb change. A primary

result of the workshop was to delineate idiopathic NSIP as a

Histologic characteristics of non-specific interstitialpneumonia

Cellular patterna

Mild to moderate interstitial chronic inflammation

Pertinent negatives: dense interstitial fibrosis, organizing pneu-

monia comprising greater than 20% of the biopsy. Lack of diffuse

pattern

Fibrosing patterna

Dense or loose interstitial fibrosis with uniform pattern

Lung architecture generally preserved

Mild or moderate chronic inflammation may also be present

Pertinent negatives: temporal heterogeneity/fibroblast foci should

be inconspicuous or absent; honeycomb change should be incon-

spicuous or absent

a Note: In both patterns the following features should be absent: features of

acute lung injury such as hyaline membranes; eosinophils; granulomas; evi-

dence of infection such as viral inclusion or organisms; dominant peribron-

chiolar disease.

Table 3



Figure 5 Non-specific interstitial pneumonia. Fibrosing NSIP is character-

ized by enlarged airspaces in which alveolar walls are fibrotic and air-

spaces are enlarged; however, the architecture of the lung is not

remodeled as seen in honeycomb fibrosis. H&E 40�.


distinct entity, recognizing that the histologic pattern of NSIP

may be encountered in a variety of settings, particularly collagen

vascular disease, hypersensitivity pneumonitis and drug toxicity

among others.1,9,13

Smoking-related interstitial lung diseases

Smoking-related interstitial lung diseases have classically

encompassed respiratory bronchiolitis-interstitial lung disease

(RB-ILD), desquamative interstitial pneumonia (DIP) and pul-

monary Langerhans cell histiocytosis (PLCH).1,14,15 In spite of

their strong association with smoking, RB-ILD and DIP were

retained in the updated classification of IIP’s as some cases of DIP

appear to be idiopathic.2 Briefly, both RB-ILD and DIP are

Figure 6 End stage “honeycomb fibrosis”. In contrast to the enlarged

airspaces of NSIP illustrated in Figure 5, honeycomb lung is characterized

by loss of normal alveolar architecture entirely and dense fibrosis sur-

rounds residual airspaces which are often lined by respiratory-type

epithelium. H&E 400�.


characterized by the presence of intra-alveolar macrophages

containing finely granular brown pigment within the cytoplasm.

In RB-ILD, the macrophages are generally present in the small

airways and immediately adjacent alveolar spaces whereas the

macrophages are present in a more or less diffuse fashion in DIP.

It should be noted that RB will be present in biopsies from

smokers in general and a diagnosis of RB-ILD refers to a specific

clinicopathologic diagnosis in which RB is the sole histologic

finding in the appropriate clinical and radiographic scenario.16,17

PLCH is characterized by areas of peribronchiolar fibrosis, often

with a “stellate” appearance. These areas variable numbers of

Langerhans cells admixed with eosinophils and pigmented

macrophages. The Langerhans cells characteristically are polyg-

onal in shape, contain nuclei with folds or grooves, and should

be positive for S-100, CD1a and Langerin by immunohisto-

chemical staining.18 These entities remain separately classified

due to differing imaging findings and response to therapy;

however, recognizing that these entities may overlap and occur

simultaneously some authors have advocated the term “smok-

ing-related ILD” to encompass these entities.19

More recently, there has been an increased focus on inter-

stitial fibrosis occurring in cigarette smokers. This has resulted

in the publication of several papers focusing on what has been

variously called “Air-space enlargement with fibrosis” and “RB-

ILD with fibrosis” among others.20,21 As background, both

emphysema and RB-ILD/DIP are defined as not being associ-

ated with significant fibrosis. However, in 2002, Fraig et al.,

described mild degrees of alveolar fibrosis in 50% of RB-ILD

cases.16 Subsequently, “RB-ILD with fibrosis” was described

by Yousem et al. in 2006.21 In a related vein, Kawabata, et al.,

described smoking related changes in the background of lung

specimens resected for cancer and Katzenstein et al. described

clinically occult interstitial fibrosis in smokers in a similar set

of patients.19,20 All of the studies described similar findings

consisting of glassy, paucicellular hyalinized fibrosis typically

occurring in areas of emphysema (Figures 7 and 8) Interest-

ingly, such patients typically exhibited obstructive symptoms

Figure 7 Smoking-related interstitial fibrosis. This photomicrograph de-

picts an area of emphysematous lung with significant interstitial fibrosis.

H&E 40�.



Figure 8 Smoking-related interstitial fibrosis. At high power, smoking-

related fibrosis is paucicellular and has a glassy appearance. H&E 400�.


related to underlying COPD rather than restrictive changes

expected of an interstitial fibrotic disease. “Smoking-related

interstitial fibrosis” was proposed for these changes by Kat-

zenstein et al.22 While this type of fibrotic change does not

appear to represent a form of IIP, awareness of this type of

fibrosis occurring in smokers is important so as not to misin-

terpret this change as a true fibrosing ILD.

Another issue in which ILD and smoking related changes may

overlap is the proposed syndrome of combined pulmonary

fibrosis and emphysema (CPFE). In this syndrome, patients have

the clinical features of tobacco smoking, severe dyspnea, “un-

expected subnormal spirometry findings”, severely impaired

transfer of carbon monoxide and hypoxemia at exercise. HRCT

typically shows centrilobular and/or paraseptal emphysema and

diffuse interstitial opacities suggestive of pulmonary fibrosis. The

pathology reported has been variable and the syndrome has been

described not only in idiopathic settings but in association with

other disorders such as collagen vascular disease. As such, at this

time this group of patients appears to represent a heterogenous

group as opposed to a distinct IIP; however, these patients do

appear to have an increased risk for the development of pul-

monary hypertension which is associated with a poor prog-

nosis.23,24 Further study and clarification of pathologic findings

in this subgroup of patients is needed.

Conclusion

In summary, since the publication of the 2002 ATS/ERS classi-

fication of IIPs the body of knowledge in certain areas has

expanded. May categories such as UIP/IPF and NSIP have un-

dergone refinement and there is increasing knowledge in regard

to the pathologic and radiographic findings in HSP and CVD-

related ILD. Patterns of lung disease not included in the 2002

classification have either been added or are at least discussed in

the update, which will be discussed elsewhere in this issue.

Finally, an increased focus on smoking related lung disease has

led to the increased recognition of interstitial fibrosis associated

with both emphysema and the spectrum of smoking related

disease such as RB-ILD/DIP and PLCH. From the pathologists


perspective it is important to discriminate smoking related

fibrosis from other forms of ILD. The syndrome of CPFE, which

appears distinctly different clinically from the type of fibrosis

associated with RB-ILD/DIP and localized emphysema, requires

clarification and study. A

REFERENCES

1 American Thoracic Society/European Respiratory Society Interna-

tional Multidisciplinary Consensus Classification of the Idiopathic

Interstitial Pneumonias. This joint statement of the American Thoracic

Society (ATS), and the European Respiratory Society (ERS) was

adopted by the ATS board of directors, June 2001 and by the ERS

Executive Committee, June 2001. Am J Respir Crit Care Med Jan 15

2002; 165: 277e304.

2 Travis W, Costabel U, Hansell D, et al. An official America Thoracic

Society/European Respiratory Society statement: update of the

classification of the idiopathic interstitial pneumonias. AJRCCM. in

press.

3 Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT

statement: idiopathic pulmonary fibrosis: evidence-based guidelines

for diagnosis and management. Am J Respir Crit Care Med Mar 15

2011; 183: 788e824.

4 Agarwal R, Jindal SK. Acute exacerbation of idiopathic pulmo-

nary fibrosis: a systematic review. Eur J Intern Med Jun 2008;

19: 227e35.

5 Churg A, Wright JL, Tazelaar HD. Acute exacerbations of fibrotic

interstitial lung disease. Histopathology Mar 2011; 58: 525e30.

6 Churg A, Muller NL, Flint J, Wright JL. Chronic hypersensitivity pneu-

monitis. Am J Surg Pathol Feb 2006; 30: 201e8.

7 Selman M, Pardo A, King Jr TE. Hypersensitivity pneumonitis: insights

in diagnosis and pathobiology. Am J Respir Crit Care Med Aug 15

2012; 186: 314e24.

8 Felicio CH, Parra ER, Capelozzi VL. Idiopathic and collagen vascular

disease nonspecific interstitial pneumonia: clinical significance of

remodeling process. Lung JaneFeb 2007; 185: 39e46.

9 Nakamura Y, Chida K, Suda T, et al. Nonspecific interstitial pneumonia

in collagen vascular diseases: comparison of the clinical character-

istics and prognostic significance with usual interstitial pneumonia.

Sarcoidosis Vasc Diffuse Lung Dis Oct 2003; 20: 235e41.

10 Park IN, Kim DS, Shim TS, et al. Acute exacerbation of interstitial

pneumonia other than idiopathic pulmonary fibrosis. Chest Jul 2007;

132: 214e20.

11 Song JW, Do KH, Kim MY, Jang SJ, Colby TV, Kim DS. Pathologic and

radiologic differences between idiopathic and collagen vascular

disease-related usual interstitial pneumonia. Chest Jul 2009; 136:

23e30.

12 Corte TJ, Copley SJ, Desai SR, et al. Significance of connective tissue

disease features in idiopathic interstitial pneumonia. Eur Respir J Mar

2012; 39: 661e8.

13 Travis WD, Hunninghake G, King Jr TE, et al. Idiopathic nonspecific

interstitial pneumonia: report of an American Thoracic Society proj-

ect. Am J Respir Crit Care Med Jun 15 2008; 177: 1338e47.

14 Caminati A, Harari S. Smoking-related interstitial pneumonias and

pulmonary Langerhans cell histiocytosis. Proc Am Thorac Soc Jun

2006; 3: 299e306.

15 Yousem SA, Colby TV, Gaensler EA. Respiratory bronchiolitis-

associated interstitial lung disease and its relationship to


http://refhub.elsevier.com/S1756-2317(13)00105-9/sref1































































Practice points

C A multidisciplinary approach is recommended for all interstitial

lung diseases

C The diagnosis of idiopathic pulmonary fibrosis requires eval-

uation of a combination of radiographic and histologic find-

ings; biopsy may not be needed in all cases

C “Air-space enlargement” in NSIP should be distinguished from

honeycomb change in UIP

C Acute exacerbation of fibrotic interstitial lung diseases,

particularly UIP, may occur and close attention should be paid

to background fibrotic changes in cases with acute findings

such as hyaline membranes or organizing pneumonia

C Close inspection for granulomas and/or Schuamann bodies

should be undertaken in cases of UIP or NSIP, particularly if a

component of bronchiolocentric disease is present

C Fibrosis secondary to cigarette smoking has a unique glassy

appearance and should be discriminated from collagenous

fibrosis of NSIP or UIP

Research directions

C Continuing research in regard to pathologic, histologic, mech-

anistic and prognostic features between idiopathic interstitial

lung disease and collagen vascular related lung disease

C Further study of risk factors and mechanisms of acute

exacerbation

C Further study of smoking-related fibrosis and clarification of

combined pulmonary fibrosis and emphysema


desquamative interstitial pneumonia. Mayo Clin Proc Nov 1989; 64:

1373e80.

16 Fraig M, Shreesha U, Savici D, Katzenstein AL. Respiratory

bronchiolitis: a clinicopathologic study in current smokers, ex-

smokers, and never-smokers. Am J Surg Pathol May 2002; 26:

647e53.

17 Myers JL, Veal Jr CF, Shin MS, Katzenstein AL. Respiratory bronchio-

litis causing interstitial lung disease. A clinicopathologic study of six

cases. Am Rev Respir Dis Apr 1987; 135: 880e4.

18 Allen TC. Pulmonary langerhans cell histiocytosis and other pulmo-

nary histiocytic diseases: a review. Arch Pathol Lab Med 2008; 132:

1171e81.

19 Katzenstein AL, Mukhopadhyay S, Zanardi C, Dexter E. Clinically

occult interstitial fibrosis in smokers: classification and significance

of a surprisingly common finding in lobectomy specimens. Hum

Pathol Mar 2010; 41: 316e25.

20 Kawabata Y, Hoshi E, Murai K, et al. Smoking-related changes in the

background lung of specimens resected for lung cancer: a semi-

quantitative study with correlation to postoperative course. Histo-

pathology Dec 2008; 53: 707e14.

21 Yousem SA. Respiratory bronchiolitis-associated interstitial lung

disease with fibrosis is a lesion distinct from fibrotic nonspecific

interstitial pneumonia: a proposal. Mod Pathol Nov 2006; 19:

1474e9.

22 Katzenstein AL. Smoking-related interstitial fibrosis (SRIF), patho-

genesis and treatment of usual interstitial pneumonia (UIP), and

transbronchial biopsy in UIP. Mod Pathol Jan 2012; 25(suppl 1):

S68e78.

23 Cottin V, Le Pavec J, Prevot G, et al. Pulmonary hypertension in pa-

tients with combined pulmonary fibrosis and emphysema syndrome.

Eur Respir J Jan 2010; 35: 105e11.

24 Jankowich MD, Rounds SI. Combined pulmonary fibrosis

and emphysema syndrome: a review. Chest Jan 2012; 141:

222e31.

DIAGNOSTIC HISTOPATHOLOGY 19:8 272 � 2013 Elsevier Ltd. All rights reserved.

















































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Classification of idiopathic interstitial pneumonias: what is new since 2002?