Honeycomb Lung History.pdf

7/29/2019 Honeycomb Lung History.pdf

1/10

AJR:196 , April 2011 773

[5], who used the term bronchiolar emphy-

sema, considered their cases to be a special

type o pulmonary emphysema.

The term honeycomb lung rst appeared

in the English literature in 1949 in a study by

Oswald and Parkinson [9]. Sixteen clinical

cases o honeycomb lung were presented in de-

tail. The cases included, as interpreted by cur-

rent medical knowledge, Langerhans cell histi-

ocytosis, lymphangioleiomyomatosis (LAM),

and probable chronic interstitial pneumonia,

which was not a disease diagnosed in that era

[9] (Fig. 2). In the denition by Oswald and

Pakinson, honeycomb lung was descriptive o

the appearance o the cut surace o the lungs

as being thin-walled cysts distributed uni-

ormly throughout the substance o both lungs,

varying in sizes up to a maximum o 1 cm in

diameter. A more comprehensive report with

a pathologic description ollowed in 1956 by

Heppleston [10], who in his practice dealt with

a wide variety o diseases and clinical back-

grounds (32 patients were coal workers). In

this report, most cases were probable chron-ic interstitial pneumonia, which also included

a small number o those with sarcoidosis, be-

rylliosis, eosinophilic granuloma, LAM, giant

cell interstitial pneumonia, scleroderma, and

even tuberculous bronchopneumonia.

Thus, beore the 1960s, honeycomb lung

was considered the macroscopic appearance

o lung diseases comprising various histo-

pathologic processes and causes, partly be-

cause physicians had little idea o identiy-

Honeycomb Lung: Historyand Current Concepts

Hiroaki Arakawa1

Koichi Honma2

Arakawa H, Honma K

1

Department o Radiology, Dokkyo Medical University,880 Kita-Kobayashi, Mibu, Tochigi, 3210293 Japan.

Address correspondence to H. Arakawa

([email protected]).

2Department o Cancer Center Pathology, Dokkyo

Medical University, Tochigi, Japan.

Cardiopulmonary Imaging Review

AJR2011; 196:773782

0361803X/11/1964773

American Roentgen Ray Society

The term honeycomb lung origi-

nated in the 19th century in Ger-

many where medicine was highly

developed in that era. We can go

back as ar as 1858 when Kessler described a

case o congenital bronchiectasis [1]. Since

then, the honeycomb appearance o the lung

was named, variously by dierent authors,

Wabenlunge (honeycomb lung), Zystenlunge

(cystic lung), Schwammlunge (spongy lung),

and Sacklunge (sacculated lung) [1, 2]. In the

German literature, honeycomb lung was usu-

ally considered a congenital malormation or

anomalous development o the lung with bron-

chiectasis [2] (Fig. 1). It seems that the term

honeycomb lung was not applied to chronic

interstitial pneumonia in Germany.

In the rst hal o the 20th century, the

idea o idiopathic pulmonary brosis (IPF)

was not yet established, and only occasional

case reports were ound, in which the authors

called their cases dierent names or only re-

ported the clinical and pathologic ndings

[36]. The amous report by Hamman andRich [3], which initially appeared in 1935,

did not use the term honeycomb lung. In

the subsequent English literature, cases o

presumed IPF were reported under the name

bronchiolar emphysema [5], pulmonary

muscular hyperplasia [4], or cystic pulmo-

nary cirrhosis [6]. Originating in the Ger-

man literature, these names were translated

into English and were discussed as a rare and

new disease entity [7, 8]. Sibert and Fisher

Keywords: CT, honeycomb lung, idiopathic interstitial

pneumonia, interstitial lung disease

DOI:10.2214/AJR.10.4873

Received April 29, 2010 ; accepted ater revision

August 28, 2010.

OBJECTIVE. Originally used to describe the macroscopic appearance o various patho-

logic processes with multiple cysts, honeycomb lung is now the term used to describe end-

stage pulmonary brosis. The purpose o this article is to discuss the history and imaging o

honeycomb lung.

CONCLUSION. Honeycomb lung is considered one o the important CT ndings in

usual interstitial pneumonia. An additional challenge or radiologists is that dierent patho-

logic processes can mimic honeycomb lung. Thereore, a precise understanding o honey-comb lung is necessary.

Arakawa and HonmaImaging o Honeycomb Lung

Cardiopulmonary ImagingReview


2/10

774 AJR:196, April 2011

Arakawa and Honma

ing the diseases in the way we do now and

partly because o the macroscopic similar-

ity o various cystic lung diseases. It was not

until 1965 that honeycomb lung was limitedto chronic interstitial pneumonia when Mey-

er and Liebow [11] suggested honeycombing

as the end-stage o chronic interst itial pneu-

monia no matter what the etiology.

Pathologic DescriptionIn the initial detailed description o honey-

comb lung, Heppleston [10] stated that the es-

sential change is the obliteration o bronchioles

by brosis or granulomata and compensatory

dilatation o neighboring bronchioles, which

orms the honeycomb appearance [10]. Thesechanges were the consistent pathologic nding

o honeycomb lung, irrespective o the cause.

A

Fig. 157-year-old womanwith bronchiectasis.A, Thin-section CTimage shows extensivebronchiectasis involving wholeright, lower lobe, simulatinghoneycomb lung. Note thatcysts are lined along bronchial

tree.

B, Photograph showsmacroscopic appearanceo surgically resected rightlower lobe. There are multiple

thin-walled cysts occupyingmost o lobe. Note that somecysts contain mucous material(arrows). Appearance wascalled Wabenlunge inGermany in late 19th and early20th centuries.

B

A

Fig. 224-year-old woman with lymphanigoleiomyomatosis (LAM).A, Thin-section CT image at level o tracheal carina shows multiple thin-wall cysts, which are mostly discrete and not subpleural, although some cysts are clustered.Appearance is not typical o honeycomb lung by current denition.B, Photomicrograph o surgically resected lung tissue reveals clusters o thin-walled cysts in subpleural area. Fibrosis is limited to area o cyst wall (arrows) and it isobvious that cysts are not result o end-stage pulmonary brosis. (Elastica-Goldner stain)

B


3/10

AJR:196 , April 2011 775

Imaging of Honeycomb Lung

In another study, honeycomb lung in scle-

roderma, dermatomyositis, Langerhans cell

histiocytosis, tuberculosis, lipoid pneumo-

nia, sarcoidosis, and IPF was studied by con-

tinuous sections o three resected lungs and

eight autopsy lungs, which were displayed in

three dimensions through photographic re-

construction [12]. The authors ound that thepathologic process in the honeycomb area

was independent o the original disease and

was undamentally diuse saccular or cystic

bronchiolectasis involving the whole lobule,

especially the terminal and respiratory bron-

chioles. The other bronchioles showed ab-

normal changes in direction, branching pat-

tern, and abrupt amputation, and there were

anastomoses between anatomically indepen-

dent bronchioles. These authors insisted that

the primary abnormality o honeycomb lung

is the brous or granulomatous process o al-

veoli and ducts, which causes the bronchi-

oles to dilate or amputate.

Radiologic Description

The early radiologic description o honey-

comb lung also indicated the various causes

and pathophysiology [13]. Honeycomb lung,

dened by visualization o multiple lucent

shadows rom 2 to 10 mm in size on a chest

radiograph, included not only diuse inter-

stitial brosis but also bronchiectasis and

even bullous emphysema [13]. The radiolog-

ic concept changed later than the patholog-

ic one. In the 1970s, the concept gradually

changed. Reed and Reeder [14] listed cys-tic bronchiectasis, eosinophilic granuloma,

pneumoconiosis, and sarcoidosis in addition

to idiopathic pulmonary brosis (Hamman-

Rich) as the common lung diseases in their

gamut o honeycomb lung. However, Felson

[15] emphasized interstitial brosis as the

basis o honeycomb lung and excluded cys-

tic bronchiectasis and bullous emphysema

rom its denition. Genereux [16] discussed

honeycomb lung rom the standpoint o the

end stage o interstitial lung disease o vari-

ous causes. This idea coincides with that o

Meyer and Liebow [11], who believed that

the lung can respond only in a stereotyped

manner to a variety o insults. Thereore,

various lung diseases can result in end-stage

lung (honeycomb lung), which is charac-

terized by cystic spaces o variable size and

extent and is caused by alveolar septal dis-solution, bronchiolectasis, and obstructive

emphysema. Signicantly, these descrip-

tions were in the era o the chest radiograph,

when the macroscopic appearance o the

lung was imaged imprecisely and thus had

substantial limitations.

Recent Denition of Honeycomb Lung

Pathology

The Fleischner Society has recently re-

vised its glossary terms, in which the patho-

logic denition o honeycomb lung ollows

that o Genereux [16] as destroyed and -

brotic lung tissue containing numerous cystic

airspaces with thick brous walls, represent-

ing the late stage o various lung diseases,

with complete loss o acinar architecture

[17]. Katzenstein [18] stated that honeycomb

lung has a characteristic gross appearance,with relatively uniormly sized cyststhat

Fig. 362-year-old man with brotic nonspecicinterstitial pneumonia (NSIP). Thin-section CT imagereveals mixture o consolidation and ground-glassopacity with traction bronchiectasis (arrows).These ectatic bronchi simulate appearance ohoneycombing. However, they can be tracked back

to bronchial tree with accompanying pulmonaryartery on contiguous images. Lung tissue intervenesbetween ectatic bronchi and cystic spaces are

not clustered. These eatures are dierent romhoneycomb lung.

A

Fig. 478-year-old woman with idiopathic pulmonary brosis (IPF).A, Initial thin-section CT image reveals multiple clustered cysts o up to 10 mm in lower lobes.B, Follow-up thin-section CT image obtained 15 months later shows obvious enlargement o each cyst, largest reaching 20 mm.

(Fig. 4 continues on next page)

B


4/10

776 AJR:196, April 2011

Arakawa and Honma

C

E

Fig. 4 (continued)78-year-old woman with

idiopathic pulmonary brosis (IPF).C, Photograph o lungs obtained at autopsyperormed 2 months ater B shows cobblestoneappearance o lung surace.D, Photograph o coronal cut surace o resectedlungs shows honeycomb lungs, closely resemblingCT appearance.E, Photomicrograph at area o honeycomb lungshows multiple cysts with dierent sizes inbackground o dense brous scar. Note presence obronchial epithelization o some o cysts (arrow). (Hand E)

D

Fig. 545-year-old woman with Langerhans cell histiocytosis. Thin-section CTimage shows discrete cystic spaces in center o right upper lobe. Some cystsare thin-walled, whereas others just look emphysematous. Most cysts sparesubpleural area and are predominant in upper lobes, which is di erent rom

typical honeycomb cyst in usual interstitial pneumonia (UIP).


5/10

AJR:196 , April 2011 777


are set in a background o dense scarring

and microscopicallyhoneycomb lung is

characterized by enlarged airspaces sur-

rounded by brosis and lined by bronchio-

lar or hyperplastic alveolar epithelium. The

combination o parenchymal collapseand

collagen deposition accounts or the major

maniestation o this lesion. According toKatzenstein, honeycomb lung is nonspecic

as to cause, and a diverse group o diseas-

es can lead to honeycombing (idiopathic in-

terstitial pneumonia [IIP], diuse alveolar

damage, asbestosis, interstitial granuloma-

tous diseases, and eosinophilic granuloma),

which corresponds to the previous under-

standing [11, 18]. In another pathology book,

Churg [19] described honeycomb lung as a

variable combination o thick-walled cysts,

which may range rom a ew millimeters to a

ew centimeters in diameter, and intervening

solid brous tissue. He continued, In ad-

dition to specic diuse diseases, localized

scars o many causes can appear as honey-

combed lung, which indicates a rather non-

specic pathologic condition [19].Pathologically, the Fleischner Society de-

nition indicates, the cysts range in size rom

a ew millimeters to several centimeters in

diameter, so they are macroscopically iden-

tiable [17]. Some researchers use the term

microscopic honeycombing to describe 1-

to 2-mm dilated bronchioles surrounded by

airless brotic lung on a pathologic specimen

[20]. On thin-section CT images, the area cor-

responds to markedly increased lung attenua-

tion with dilated bronchioles and is thereore

dierent rom the macroscopic honeycomb

lung. Whether the pathologic process that oc-

curs in the microscopic honeycombing has

a similar clinical and pathophysiologic signi-

icance to that o (macroscopic) honeycomb

lung is still to be determined.

Radiology

A recent denition o honeycomb lung in

radiology is based on thin-section CT, which

can image the lungs close to their macroscopic

appearance [21]. The initial denition by the

Fleischner Society, which was published in

1984, stated that honeycomb lung is a num-

ber o closely approximated ring shadows

A

Fig. 668-year-old man with combined emphysemaand chronic interstitial pneumonia, who developedsquamous cell carcinoma.A, Thin-section CT image o lung tumor revealsmultiple thin-walled cysts and emphysema. Ground-glass opacity is noted adjacent to cystic area(arrows), indicating presence o chronic interstitialpneumonia. Cystic spaces are confuent and arelarger with thinner walls than those o honeycomblung. This is considered coexistence o emphysemaand chronic interstitial pneumonia and nothoneycomb lung.B, Photograph o cut surace (corresponding to CT

slice) o surgically resected let lower lobe showsmultiple cysts o various sizes, giving appearance ohoneycombing.C, Photomicrograph o cystic space showsdestruction and brosis o pulmonary parenchyma,with varying-sized cyst, which is separated romnormal lung by interlobular septa (asterisks). (H and E)D, Photomicrograph shows presence o broblasticoci (arrow), which is compatible with interstitialbrosis. (Elastica-Goldner stain)

B

C D


6/10

778 AJR:196, April 2011

Arakawa and Honma

representing air spaces 510 mm in diameterwith walls 23 mm thickwhose occurrence

implies end-stage lung [22], which is in con-

cert with the statement by Meyer and Liebow

[11] and Genereux [16]. The second statement

by the Fleischner Society, which was published

in 1996, said, Clustered cystic air space, usu-

ally o comparable diameters on the order o

0.31.0 cm but as much as 2.5 cm, usually is

subpleural and characterized by well-dened

walls, which are oten thicka CT eature o

diuse pulmonary brosis [23]. These earlier

denitions, which were in the era o the chest

radiograph in the rst version and o CT in the

second version, are almost the same exceptor the size and location. In the latest version

rom the Fleischner Society, honeycomb lung

is dened as clustered cystic air spaces, typi-

cally o comparable diameters on the order o

310 mm but occasionally as large as 2.5 cm

usually subpleural and characterized by well-

dened walls [17]. The size and wall thick-

ness o the cysts vary among the authors who

use the term. However, the cystic air spaces

o honeycomb lung tend to share walls [24].

This means that traction bronchiolectasis with

intervening lung should not be called honey-

combing (Fig. 3). Because o the small size o

the cyst, diagnosis should be perormed with

thin-section CT [25]. Although dierent dis-

ease processes result in the same pathologic

and radiologic appearance, recent understand-

ing indicates that honeycombing is oten con-

sidered specic or pulmonary brosis and is

an important criterion in the diagnosis o usu-

al interstitial pneumonia (UIP), and thus the

term should be used with care [because] it may

directly impact patient care [17].

The latest denition emphasizes the im-portance o honeycombing as the diagnostic

criterion o UIP. This emphasis originated

rom the recent consensus statement about

idiopathic pulmonary brosis published in

2000 by American Thoracic Society and Eu-

ropean Respiratory Society, which empha-

sized the clinical relevance o discriminating

UIP rom other IIP [25]. Among idiopathic

interstitial pneumonia, IPF is a progressive

disease, oten with acute exacerbation, and

shows ar worse prognosis than other chronic

interstitial pneumonia [26]. Although a new

antibrotic drug has emerged as a possible

treatment option or IPF [27], the prognosisis still regarded as poor [28].

Progression of Honeycomb Lung

Because honeycomb lung is the end stage

o interstitial pneumonia, there must be an ab-

normality that precedes it. In the case o UIP,

honeycomb lung is preceded by the presence

o patchy ground-glass opacity and reticu-

lation within a secondary lobule [29]. Over

time, intralobular reticulation increases and

traction bronchiolectasis gradually appears in

the area o the ground-glass opacity while the

ground-glass opacity diminishes and nally

results in honeycombing [29, 30]. The earliest

CT abnormality o UIP is poorly understood.

In one report o 14 cases o silicosis that de-

veloped chronic interstitial pneumonia with

honeycombing, the earliest abnormality was

aint ground-glass opacity or, less requently,

coarse reticulation [30]. However, this study

was perormed with 10-mm slice thickness.

The speed o progression o honeycomb

lung is poorly understood. In a series o 29 IPF

patients, the progression o honeycomb lungranged rom 0% to 11% o the lungs per month

(median, 0.4%) and was astest in the low-

er lobes [29]. In another series o 14 patients

with chronic interstitial pneumonia and silico-

sis observed or a median o 15.4 years, nor-

mal or near-normal lung progressed to hon-

eycomb lung within a median o 12.1 years

(range, 3.719.1 years) [30]. It is presumed

that a long asymptomatic period exists beore

honeycomb lung develops and the patient be-

comes symptomatic. With the common use o

CT examinations in this era o MDCT, cases

o IPF without honeycomb lung are expected

to be increasingly ound, which challengesradiologists in CT diagnosis.

Although most cases o honeycomb lung

are seen in chronic lung disease, it can also

occur in a minority o patients with acute

interstitial pneumonia and diuse alveolar

damage [31, 32]. This disease is progressive

by the day or week, and the result is oten a-

tal. Honeycomb lung is not the initial eature,

but it can occur as early as 1 week ater the

onset o symptoms [31].

The size o the honeycomb cyst usually in-

creases during ollow-up [33]. In two autopsy

series o patients with honeycombing o UIP,

stenosis or abrupt angulations o bronchioleand slitlike structures between the cysts and

bronchioles were ound, which were regard-

ed as the causes o progressive enlargement o

honeycomb cysts [12, 33] (Fig. 4). In another

study o 97 patients with end-stage lung dis-

ease, patients underwent paired inspiratory

and expiratory volume scanning o the lung,

and the size o honeycomb cysts was evaluated

using multiplanar reormation [34]. The large

A

Fig. 756-year-old man with emphysema whodeveloped interstitial pneumonia during ollow-up.A, Thin-section CT image shows emphysema inperiphery o right lower lobe. There is minimumincrease in lung attenuation associated withemphysematous area.B, Thin-section CT image obtained 5 years latershows cluster o multiple cysts in area o previousemphysema. This appearance mimics honeycomb

lung. However, it is not end-stage o chronic brosinginterstitial pneumonia but superimposition o ground-glass opacity on emphysema.

B


7/10

AJR:196 , April 2011 779


honeycomb cysts (mean, 20.6 mm; SD, 10.7

mm) tended to have thinner walls and did not

communicate with the airways and thus did

not change in size during orced exhalation,

whereas the small cysts (mean, 2.7 mm; SD,4.3 mm) did have communication with the air-

ways and their size changed on expiration [34].

The data suggest that the progressive enlarge-

ment o honeycomb cysts is partly due to air

trapping by the check-valve mechanism.

Honeycomb Lung as the CT Criterion of UIP

Honeycombing is oten considered spe-

cic to pulmonary brosis and is an impor-

tant criterion in the diagnosis o UIP [17]. By

denition, however, it is not the specic CT

nding o UIP, although honeycombing is

the common nding o UIP.

In previous literature, honeycombing wasidentied in 41100% o UIP, depending on

the reported series [3544]. In one report o

168 cases o suspected IIP, the sensitivity and

specicity o the presence o honeycombing

in the diagnosis o UIP were 90% and 86%,

respectively [45]. Nonspecic interstitial

pneumonia (NSIP) and desquamative intersti-

tial pneumonia (DIP), which are the chronic

interstitial pneumonias o IIP and are the im-

portant dierential diagnostic considerations,

show honeycombing in 030% and 4.339%,

respectively [37, 38, 4648]. In acute intersti-

tial pneumonia, the requency is lower, rang-

ing rom 6% to 14% [31, 32, 49].Honeycomb lung in UIP is usually subpleu-

ral and is predominant in posterior and lower

lobes [29, 35, 50]. This characteristic distri-

bution distinguishes UIP rom other diseases

with honeycomb lung. In a study o 61 various

end-stage lung diseases (26 UIP, nine sarcoido-

sis, eight Langerhans cell histiocytosis, ve as-

bestosis, our silicosis, our chronic hypersensi-

tivity pneumonitis, three LAM, one berylliosis,

A

Fig. 864-year-old man with silicosis and chronic interstitial pneumonia.A, Initial CT image shows slight increase in lung at tenuation in both lung bases (arrows).B, In CT image obtained 8 years later, ground-glass opacity is obvious and multiple lung cysts are identied in area o ground-glass opacity, giving appearance oemphysematous cysts (arrows).C, CT image obtained 5 years ater B shows urther progression o ground-glass opacity and increased number and size o lung cysts. These cysts are thin-walled andspare subpleural zone, although some cysts are clustered. CT nding is dierent rom honeycomb lung o usual interstitial pneumonia (UIP).D, Photomicrograph o lung specimen shows multiple lung cysts in area o interstitial brosis (arrowheads). Appearance is dieren t rom honeycomb lung in UIP.Pathologic diagnosis was also dierent rom typical UIP pattern. Arrows indicate pleural surace. (Elastic-Goldner stain)

B

C D


8/10

780 AJR:196, April 2011

Arakawa and Honma

and one talcosis), the characteristic distribution

o honeycombing made it possible to diagnose

UIP in 88% o the cases, with a high degree o

condence in 67% [51] (Fig. 5).

In addition to the distribution, the extent

o honeycomb cyst is another important con-

sideration when diagnosing UIP. It has been

reported that the extent o honeycombing

ranged rom 3% to 21% o the lung parenchy-

ma in UIP [3544]. On the other hand, the

extent o honeycombing in NSIP and DIP is

reported as 0.33.7% and 0.710% o the lung

parenchyma, respectively [37, 38, 4648]. In

these reports, both the requency and extent

are signicantly higher in UIP than in DIP or

NSIP, although there seems to be no thresholdthat discriminates UIP rom other IIP.

Problems in Diagnosing

Honeycomb Lung

There are several diculties in the diagno-

sis o honeycomb lung. One is the denition

o the terminology and the others are asso-

ciated with radiographic diagnosis with CT.

The problem o diagnosis originates rom the

historical change o the concept and the di-

erent circumstances in which it is made. In

the previous literature, honeycombing meant

nonspecic cystic pulmonary conditions, in-

cluding bronchiectasis and congenital cysticlung disease. However, in the recent litera-

ture, its use is limited mostly to the end-stage

lung with interstitial brosis.

Other problems aect the CT diagnosis o

honeycomb lung in cases with chronic interst i-

tial pneumonia [52]. Although the denition is

straightorward, diagnosing honeycomb lung

in IPF or UIP is sometimes not easy or radi-

ologists. For instance, in a study o 314 cases

o IPF, the interobserver agreement regarding

the presence o honeycomb lung ranged rom

0.21 to 0.31, which indicates rather poor agree-

ment [36]. This variation could originate rom

the varied appearance o cystic structures in

chronic interstitial pneumonia, in which there

can be traction bronchiolectasis, subpleural

cysts or bulla, and emphysema, especially o

the paraseptal type. Located in the subpleu-

ral area, all these structures appear cystic and

oten have walls. The coexistence o emphy-

sema is reported in the subset o patients with

IPF, which is rather a common phenomenon

because both diseases are associated with cig-

arette smoking [5356]. Although emphyse-

ma is pathologically dened as loss o lungparenchyma without brosis, brosis can co-

exist in the area with emphysema [57] (Fig. 6).

Although such brosis may be dierent rom

UIP [58], the presence o this brosis can be

a risk actor o acute exacerbation during cy-

totoxic drug treatment [59] and ater pulmo-

nary surgery [60].

Emphysema and cystic spaces can be

challenging in the presence o overlapping

ground-glass opacity [47]. In a study o 34

patients with either UIP or NSIP and em-

physema, emphysematous lung or cystic ar-

eas were misdiagnosed as honeycombing

in three cases [47]. This situation can oc-cur with pneumonia in emphysematous lung

but more problematic is the development o

chronic interstitial pneumonia in emphyse-

matous lung during ollow-up (Fig. 7). NSIP

and DIP, which show predominantly ground-

glass opacity, might show a honeycomb ap-

pearance i the abnormality involves the em-

physematous area and thus would likely be

misdiagnosed as UIP [47].

Furthermore, emphysema and interstitial

brosis develop and progress simultaneously

in the same lung area [61] (Fig. 8). The end

result is similar to honeycomb lung, which is

oten relatively thin walled and presents a di-

agnostic challenge to radiologists.

Finally, paraseptal emphysema, which is one

o the types o emphysema, has denite walls,

is located subpleurally, and is oten clustered

(Fig. 9). Pathologically, paraseptal emphyse-

ma is oten accompanied by brosis in its walls

[62]. There are cases that show paraseptal em-

physema in the upper and middle lobes, al-

though there is typical honeycomb lung in

the lower lobes. In these cases, these dier-

ent pathologic processes are oten continuouswith each other in the subpleural zone. Thus,

dierentiating the two is almost impossible.

It should be kept in mind that honeycomb

lung is the end stage o pulmonary brosis.

Thus, the development o ground-glass opac-

ity in the area o emphysema should not be

called honeycomb lung. However, in cases o

the simultaneous progression o brosis and

airspace enlargement, it might be dicult to

reject the term honeycomb lung.

Future of CT Diagnosis of

Honeycomb Lung

Because the term honeycomb lung is close-ly linked with the concept o the disease and

with the classication o idiopathic interstitial

pneumonia, the denition and clinical mean-

ing o honeycomb lung have changed and may

change rom the present denition in the uture.

In the meantime, it is important to use the term

in consensus, and when it is used, interpreters

should have a unanimous opinion and image o

what is meant by honeycomb lung.

A

Fig. 962-year-old man with emphysema andchronic interstitial pneumonia.A, Thin-section CT image at lung base showshoneycomb lung.B, Thin-section CT image at tracheal carina showsparaseptal emphysema with varied thickness o cystwall. Most anterior cysts appear similar to those olung base, showing similarity o honeycomb cyst andparaseptal emphysema.

B


9/10

AJR:196 , April 2011 781


Disagreement concerning the CT diagno-

sis o honeycomb lung could partly be ex-

plained by the lack o prespecied consensus,

and thus reerence images, such as the Inter-

national Labor Oce classication o pneu-

moconiosis, are considered to improve the

interobserver agreement [36]. Actually, reer-

ence images should be used so that we have aunanimous CT diagnosis o honeycomb lung

in diagnosing IPF. Because the nal goal is

to identiy those patients who are likely to

show progressive disease and die within sev-

eral years, the prespecied pattern o honey-

combing should be revised on the basis o the

results o the prospective observation that will

be undertaken, depending on the prespecied

consensus. The revision is an urgent task or

radiologists considering that the presence and

extent o honeycombing is the most important

thin-section CT nding in the correct diagno-

sis o UIP [3941, 43, 44, 47].

References

1. Bargon G. Zur Pathogenese der Wabenlunge. Be-

itr Pathol Anat1955; 115:452469

2. Otto A, Otto H. Einiges uber Zysten und Waben-

lungen.Z Gesamte Inn Med1956; 11:505511

3. Hamman L, Rich A. Fulminating diuse intersti-

tial brosis o the lungs. Trans Am Clin Climatol

Assoc 1935; 151:154163

4. Rubenstein L, Gutstein WH, Lepow H. Pulmo-

nary muscular hyperplasia (muscular cirrhosis o

the lungs).Ann Intern Med1955; 42:3643

5. Siebert FT, Fisher ER. Bronchiolar emphysema:

so-called muscular cirrhosis o the lungs. Am JPathol 1957; 33:11371161

6. Hirsheld HJ, Krainer L, Coe GC. Cystic pulmo-

nary cirrhosis (bronchiolar emphysema). Dis

Chest1962; 42:107110

7. von Stossel E. Uber Muskulare Cir rhose der

Lunge.Beitr Klin Tuberk1937; 90:429442

8. Davidsohn C. Uber Muskulare Lungencirrhose.

Berl Klinwchnschr1907; 44:33

9. Oswald N, Parkinson T. Honeycomb lungs. QJM

1949; 18:120

10. Heppleston AG. The pathology o honeycomb

lung. Thorax1956; 11:7793

11. Meyer EC, Liebow AA. Relationship o intersti-

tial pneumonia honeycombing and atypical epi-

thelial prolieration to cancer o the lung. Cancer

1965; 18:322351

12. Pimentel JC. Tridimensional photographic recon-

struction in a study o the pathogenesis o honey-

comb lung. Thorax1967; 22:444452

13. Johnson TH Jr. Radiology and honeycomb lung

disease.Am J Roentgenol Radium Ther Nucl Med

1968; 104:810821

14. Reed JC, Reeder MM. Honeycomb lung (intersti-

tial brosis).JAMA 1975; 231:646647

15. Felson B. Chest Roentgenology. Philadelphia, PA:

Saunders, 1973

16. Genereux GP. The end-stage lung: pathogenesis,

pathology, and radiology. Radiology 1975;

116:279289

17. Hansell DM, Bankier AA, MacMahon H, McLoud

TC, Muller NL, Remy J. Fleischner Society: glos-

sary o terms or thoracic imaging. Radiology

2008; 246:697722

18. Katzenstein AL. Idiopathic interstitial pneumo-

nia. In: Katzenstein AL. Kazenstein and Askins

surgical pathology of non-neoplastic lung dis-

ease. Philadelphia, PA: Saunders, 2006:5184

19. Churg AM. Lung biopsy, lung resection, and autopsy

lung specimens. In: Churg AM, Myers JL, Tazelaar

HD, Wright JL, eds. Thurlbechs pathology of the

lung. New York, NY: Thieme, 2005:95108

20. Nishimura K, Kitaichi M, Izumi T, Nagai S, Ka-

naoka M, Itoh H. Usual interstitial pneumonia:

histologic correlation with high-resolution CT.

Radiology 1992; 182:337342

21. Murata K, Khan A, Herman PG. Pulmonary pa-

renchymal disease: evaluation with high-resolu-

tion CT.Radiology 1989; 170:629635

22. Tuddenham WJ. Glossary o terms or thoracic

radiology: recommendations o the Nomenclature

Committee o the Fleischner Society. AJR 1984;

143:509517

23. Austin JH, Muller NL, Friedman PJ, et al. Glos-

sary o terms or CT o the lungs: recommenda-

tions o the Nomenclature Committee o the

Fleischner Society.Radiology 1996; 200:327331

24. Webb WR, Muller NL, Naidich DP. Standardized

terms or high-resolution computed tomographyo the lung: a proposed glossary. J Thorac Imag-

ing 1993; 8:167175

25. Idiopathic pulmonary brosis: diagnosis and

treatmentinternational consensus statement o

the American Thoracic Society and the European

Respiratory Society.Am J Respir Crit Care Med

2000; 161:646664

26. Kondoh Y, Taniguchi H, Kawabata Y, Yokoi T,

Suzuki K, Takagi K. Acute exacerbation in idio-

pathic pulmonary brosis: analysis o clinical and

pathologic ndings in three cases. Chest 1993;

103:18081812

27. Taniguchi H, Ebina M, Kondoh Y, et al. Pireni-

done in idiopathic pulmonary brosis.Eur Respir

J2010; 35:821829

28. Collard HR, Moore BB, Flaher ty KR, et al. Acute

exacerbations o idiopathic pulmonary brosis.

Am J Respir Crit Care Med2007; 176:636643

29. Akira M, Sakatani M, Ueda E. Idiopathic pulmo-

nary brosis: progression o honeycombing at

thin-section CT.Radiology 1993; 189:687691

30. Arakawa H, Fujimoto K, Honma K, et al. Progres-

sion rom near-normal to end-stage lungs in

chronic interstitial pneumonia related to silica ex-

posure: long-term CT observations. AJR 2008;

191:10401045

31. Johkoh T, Muller NL, Taniguchi H, et al. Acute

interstitial pneumonia: thin-section CT ndings

in 36 patients.Radiology 1999; 211:859863

32. Ichikado K, Suga M, Muller NL, et al. Acute in-

terstitial pneumonia: comparison o high-resolu-

tion computed tomography ndings between sur-

vivors and nonsurvivors. Am J Respir Crit Care

Med2002; 165:15511556

33. Mino M, Noma S, Kobashi Y, Iwata T. Serial

changes o cystic air spaces in brosing alveolitis:

a CTpathological study. Clin Radiol 1995;

50:357363

34. Johkoh T, Muller NL, Ichikado K, et al. Respira-

tory change in size o honeycombing: inspiratory

and expiratory spiral volumetric CT analysis o 97

cases.J Comput Assist Tomogr1999; 23:174180

35. Hunninghake GW, Lynch DA, Galvin JR, et al.

Radiologic ndings are strongly associated with a

pathologic diagnosis o usual interstitial pneumo-

nia. Chest2003; 124:12151223

36. Lynch DA, David Godwin J, Sarin S, et al. High-

resolution computed tomography in idiopathic

pulmonary brosis: diagnosis and prognosis.Am

J Respir Crit Care Med2005; 172:488493

37. Silva CI, Muller NL, Hansell DM, Lee KS, Nich-

olson AG, Wells AU. Nonspecic interstitial

pneumonia and idiopathic pulmonary brosis:

changes in pattern and distribution o disease over

time.Radiology 2008; 247:251259

38. Tsubamoto M, Muller NL, Johkoh T, et al. Patho-

logic subgroups o nonspecic interstitial pneu-

monia: dierential diagnosis rom other idiopath-ic interstitial pneumonias on high-resolution

computed tomography. J Comput Assist Tomogr

2005; 29:793800

39. Elliot TL, Lynch DA, Newell JD Jr, et al. High-

resolution computed tomography eatures o non-

specic interstitial pneumonia and usual intersti-

tial pneumonia. J Comput Assist Tomogr2005;

29:339345

40. Johkoh T, Muller NL, Cartier Y, et al. Idiopathic

interstitial pneumonias: diagnostic accuracy o

thin-section CT in 129 patients.Radiology 1999;

211:555560

41. Nagai S, Kitaichi M, Itoh H, Nishimura K, Izumi

T, Colby T. Idiopathic nonspecic interstitial

pneumonia/brosis: comparison with idiopathic

pulmonary brosis and BOOP.Eur Respir J1998;

12:10101019

42. Sumikawa H, Johkoh T, Colby TV, et al. Com-

puted tomography ndings in pathological usual

interstitial pneumonia: relationship to survival.

Am J Respir Crit Care Med2008; 177:433439

43. Sumikawa H, Johkoh T, Ichikado K, et al. Usual

interstitial pneumonia and chronic idiopathic in-


10/10

782 AJR:19 6, April 2011

Arakawa and Honma

terstitial pneumonia: analysis o CT appearance

in 92 patients.Radiology 2006; 241:258266

44. Shin KM, Lee KS, Chung MP, et al. Prognostic

determinants among clinical, thin-section CT,

and histopathologic ndings or brotic idiopathic

interstitial pneumonias: tertiary hospital study.

Radiology 2008; 249:328337

45. Flaherty KR, Toews GB, Travis WD, et al. Clini-

cal signicance o histological classication o

idiopathic interstitial pneumonia. Eur Respir J

2002; 19:275283

46. Travis WD, Hunninghake G, King TE Jr, et al.

Idiopathic nonspecic interstitial pneumonia: re-

port o an American Thoracic Society project.Am

J Respir Crit Care Med2008; 177:13381347

47. Akira M, Inoue Y, Kitaichi M, Yamamoto S, Arai

T, Toyokawa K. Usual interstitial pneumonia and

nonspecic interstitial pneumonia with and with-

out concurrent emphysema: thin-section CT nd-

ings.Radiology 2009; 251:271279

48. Hartman TE, Primack SL, Kang EY, et al. Dis-

ease progression in usual interstitial pneumonia

compared with desquamative interstitial pneumo-

nia: assessment with serial CT. Chest 1996;

110:378382

49. Primack SL, Hartman TE, Ikezoe J, Akira M,

Sakatani M, Muller NL. Acute interstitial pneu-

monia: radiographic and CT ndings in nine pa-

tients.Radiology 1993; 188:817820

50. Nagao T, Nagai S, Hiramoto Y, et al. Serial evalu-

ation o high-resolution computed tomography

ndings in patients with idiopathic pulmonary -

brosis in usual interstitial pneumonia.Respiration

2002; 69:413419

51. Primack SL, Hartman TE, Hansell DM, Muller

NL. End-stage lung disease: CT ndings in 61 pa-

tients.Radiology 1993; 189:681686

52. Galvin JR, Frazier AA, Franks TJ. Collaborative

radiologic and histopathologic assessment o -

brotic lung disease.Radiology 2010; 255:692706

53. Cottin V, Nunes H, Brillet PY, et al. Combined pul-

monary brosis and emphysema: a distinct under-

recognised entity.Eur Respir J2005; 26:586593

54. Grubstein A, Bendayan D, Schactman I, Cohen

M, Shitrit D, Kramer MR. Concomitant upper-

lobe bullous emphysema, lower-lobe interstitial

brosis and pulmonary hypertension in heavy

smokers: report o eight cases and review o the

literature.Respir Med2005; 99:948954

55. Doherty MJ, Pearson MG, OGrady EA, Pellegrini

V, Calverley PM. Cryptogenic brosing alveolitis

with preserved lung volumes. Thorax 1997;

52:9981002

56. Wiggins J, Str ickland B, Turner-Warwick M.

Combined cryptogenic brosing alveolitis and

emphysema: the value o high resolution comput-

ed tomography in assessment. Respir Med 1990;

84:365369

57. Niewoehner DE, Kleinerman J, Rice DB. Pathologic

changes in the peripheral airways o young cigarette

smokers.N Engl J Med1974; 291:755758

58. Katzenstein AL, Mukhopadhyay S, Zanardi C,

Dexter E. Clinically occult interstitial brosis in

smokers: classication and signicance o a sur-

prisingly common nding in lobectomy speci-

mens.Hum Pathol 2010; 41:316325

59. Kudoh S, Kato H, Nishiwaki Y, et al. Interstitial

lung disease in Japanese patients with lung can-

cer: a cohort and nested case-control study.Am J

Respir Crit Care Med2008; 177:13481357

60. Kawabata Y, Hoshi E, Murai K, et al. Smoking-

related changes in the background lung o speci-

mens resected or lung cancer: a semiquantitative

study with correlation to postoperative course.

Histopathology 2008; 53:707714

61. Arakawa H, Johkoh T, Honma K, et al. Chronic

interstitial pneumonia in silicosis and mix-dust

pneumoconiosis: its prevalence and comparison

o CT ndings with idiopathic pulmonary brosis.

Chest2007; 131:18701876

62. Wright JL. Chronic airfow obstruction. In: Churg

AM, Myers JL, Tazelaar HD, Wright JL, eds.

Thurlbecks pathology of the lung. New York,

NY: Thieme, 2005:686687

Documents

Honeycomb Lung History.pdf