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□ CASE REPORT □

Organizing Pneumonia Complicated by Cyst andPneumothorax Formation

Tsukasa Kadota 1, Kenichiro Shimizu 1, Chikako Tsurushige 1, Makoto Kawaishi 1,

Jun Araya 1, Katsutoshi Nakayama 1, Kazuyoshi Kuwano 1 and Hiroshi Hano 2

Abstract

We present a case of organizing pneumonia complicated by pneumothorax in association with cyst forma-

tion that developed during corticosteroid treatment. Although it has been reported that the check-valve

mechanism is a plausible cause of cyst and pneumothorax formation in patients with organizing pneumonia,

the details of the corresponding pathological changes that occur in air-trapping have not been elucidated. A

pathological examination of lung specimens obtained with video-assisted thoracoscopic surgery suggested

that granulation tissues plugging the bronchiole lumens might be a potential cause of the check-valve mecha-

nism in this case. In this report, we also reviewed eight other cases of organizing pneumonia with pneumot-

horax or cyst formation.

Key words: organizing pneumonia, cyst, pneumothorax, check-valve mechanism

(Intern Med 51: 3155-3158, 2012)(DOI: 10.2169/internalmedicine.51.8319)

Introduction

Organizing pneumonia (OP) complicated by pneumotho-

rax formation concomitantly with cyst formation is rare.

Eight cases of OP complicated by cyst or pneumothorax for-

mation have been previously reported; however, the causal

mechanisms of the development of cyst and pneumothorax

formation related to OP have not been clarified (1-8). Al-

though air-trapping caused by the check-valve mechanism is

thought to be a plausible mechanism of cyst and pneumot-

horax formation, the details of the corresponding pathologi-

cal changes that occur in air-trapping have not been eluci-

dated. We herein report a case of OP complicated by cyst

and pneumothorax formation in which the pathological ex-

amination of lung specimens obtained with video-assisted

thoracoscopic surgery (VATS) suggested that granulation tis-

sues plugging the bronchiole lumens might be a potential

cause of the check-valve mechanism. We also reviewed

eight other reported cases of organizing pneumonia with

pneumothorax or cyst formation.

Case Report

A 37-year-old Japanese man was referred from another

hospital and was admitted to our hospital due to pneumonia

that was refractory to conventional antibiotic treatment. Four

weeks prior to admission, the patient presented with fever, a

dry cough and respiratory distress. Chest X-rays performed

at that time showed multiple areas of consolidation in the

right lung field, and a diagnosis of pneumonia was thus sus-

pected. The patient had been treated unsuccessfully with

several antibiotics (clarithromycin at a dose of 400 mg/day

for three days, then levofloxacin at a dose of 500 mg/day

for three days followed by meropenem at a dose of 1 g/day

for 14 days, garenoxacin at a dose of 400 mg/day for five

days and minocycline at a dose of 200 mg/day for nine

days). The patient also presented with arthralgia of multiple

joints; however, he denied morning stiffness or Raynaud’s

phenomenon. He had no medical history of allergies or pre-

vious medications and had smoked a half-pack of cigarettes

daily for 15 years.

A physical examination revealed hypoxemia with an oxy-

gen saturation of 95% (nasal O2 at 1 L/min). Auscultation of

１Department of Respiratory Medicine, Jikei University Hospital, Japan and ２Department of Pathology, Jikei University Hospital, Japan

Received for publication June 19, 2012; Accepted for publication August 16, 2012

Correspondence to Dr. Tsukasa Kadota, tkskdt@jikei.ac.jp

Intern Med 51: 3155-3158, 2012 DOI: 10.2169/internalmedicine.51.8319

3156

Figure　1.　(a): Chest X-ray revealed consolidations in the right lower and the left middle lung fields and a right-sided pleural effusion. (b): Computed tomography scanning showed extensive infiltra-tions on the right side and air bronchogram in the lower lobes with an interstitial pattern. (c): CT scanning on the 11th hospital day. A right-sided pneumothorax and cyst close to S8 with air fluid in-terface were found. (d): Chest X-ray on the 35th day from the steroid therapy. Bilateral consolida-tion was remarkably improved.

the lungs revealed decreased respiratory sounds in the right

lower lobe. The patient complained of joint pain in the left

cubital joint, right shoulder joint and bilateral knee joints on

exertion; however, no swelling or tenderness were demon-

strated. The laboratory findings showed elevated levels of C-

reactive protein (CRP) (9.75 mg/dL), a white blood cell

count of 8,600/μL with 74% neutrophils, a rheumatoid fac-

tor level of 309.1 IU/mL and an anti-CCP antibody level of

1,070.0 U/mL. The pleural effusion was exudative with a

white blood cell count of 8,100/μL (neutrophils: 74.8%,

eosinophils: 1.5%), a rheumatoid factor level of 386.0 IU/

mL, a glucose level of 46 mg/dL and low levels of comple-

ment. The results of bacteriological examinations for blood,

urine and sputum were all negative.

Chest X-rays showed multiple areas of consolidation in

the right lower and left middle lung fields and a right-sided

pleural effusion (Fig. 1a). A computed tomography scan

showed extensive dense infiltration on right S4, S8, S9 and

S10 and consolidation with an air bronchogram accompa-

nied by ground glass opacity in the bilateral lower lobes

(Fig. 1b). Bronchoalveolar lavage fluid (BALF) obtained

from the rt.B4a demonstrated an increased total cell count

(3.28×106 cells/mL) with a marked increase in the propor-

tion of lymphocytes (66.2%) and a normal CD4/CD8 ratio

of 1.52. These findings were compatible with a diagnosis of

secondary OP suspected to be undifferentiated connective

tissue disease, particularly rheumatoid arthritis.

Treatment with corticosteroid therapy (1 mg/kg/day, total

of 55 mg/day) was started, after which the patient’s symp-

toms and X-ray findings gradually improved. However, on

the 7th day of steroid therapy, a right-sided pneumothorax

and small cysts (right S8) were found on chest X-ray and

chest CT (Fig. 1c). Hence, a chest drainage tube was in-

serted on the same day. The air leak persisted for more than

five days and a complicated hemothorax developed. There-

fore, we considered the option of surgical resection to treat

the refractory pneumothorax. Video-assisted thoracoscopic

bullectomy was performed on the 15th day of steroid ther-

apy. A thoracoscopic examination demonstrated that the air

leak point was located near the cyst, which was confirmed

by clamping the cyst. The pathological findings of the speci-

mens obtained with VATS revealed a cystic lesion with lung

tissue laceration and fresh bleeding (Fig. 2a), granulation

tissue plugging the bronchiole lumens in close proximity to

the cystic changes (Fig. 2b) and granulation tissue in the al-

veoli and alveolar ducts (Figs. 2c, 2d). The results of the

pathological examination were compatible with a diagnosis

of OP. Following the VATS, the prednisolone dose was

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Figure　2.　Photomicrographs of the following specimens: (a) A cystic lesion with laceration of the lung tissue and fresh bleeding, Masson’s trichrome stain; (b) granulation tissue plugging in the lu-men of bronchiole, Masson’s trichrome stain, ×100; (c) granulation tissue in the alveoli and alveolar duct, Hematoxylin and Eosin staining, ×100; and (d) granulation tissue in the alveoli and alveolar duct, Masson’s trichrome stain, ×100.

(a)

(c) (d)

(b)(a)

(c) (d)

(b)

gradually tapered by 5 mg every two weeks. The patient’s

symptoms and X-ray consolidation improved remarkably. He

was free of relapse and exacerbation during the reduction of

the corticosteroid treatment (Fig. 1d).

Discussion

We herein present a case of OP complicated by cystic le-

sions and a pneumothorax that developed after steroid treat-

ment. Although there are a few cases of OP complicated by

either cyst or pneumothorax formation, the concomitant

complication of cyst and pneumothorax formation underly-

ing OP has never been reported. The characteristic features

of the eight previously published case reports and the pre-

sent case are summarized in Table (1-8). These cases were

classified on the basis of a pathological diagnosis of OP, its

diagnostic method, the presence of cysts or a pneumothorax,

suspected mechanisms and steroid use. This classification re-

vealed interesting characteristics. First, the patients in all

cases were men. Second, seven of nine patients were diag-

nosed with cryptogenic OP. However, we speculate that the

present case include antecedent pulmonary involvement of

rheumatoid arthritis. Although the present patient did not

fulfill the classification criteria for rheumatoid arthritis, the

articular symptoms, positivity for anti-CCP and rheumatoid

factor and high rheumatoid factor level in the exudative

pleural effusion observed in the case support that possibility.

Third, only the present case was complicated by both

cyst and pneumothorax formation. Moreover, some

cases (1, 4, 6) were complicated by either cyst or pneumot-

horax formation after the initiation of corticosteroid therapy,

whereas in the other cases (2, 7), the cysts disappeared after

the initiation of corticosteroid therapy. Therefore, we sur-

mise that corticosteroid therapy administration could be one

risk factor for pneumothorax formation by making the tissue

fragile, as with dissolving OP tissue. Pneumothorax forma-

tion might be associated in some ways with a delayed

wound healing process caused by corticosteroid therapy. The

exact mechanism underlying the development of both a cyst

and a pneumothorax in our case remains uncertain. One

plausible explanation might be the check-valve mechanism,

in which obstruction of the bronchioles increases alveolar

pressure during exhalation, resulting in initial overinflation,

the formation of a cyst with pulmonary tissue laceration

and, finally, rupture of the pleural tissue. Air from the rup-

tured alveolus continues to move through the mediastinal

parietal pleura into the pleural space, leading to pneumotho-

rax formation (9). Previous reports (2, 5, 7) have already

discussed the role of the check-valve mechanism in the de-

velopment of cysts and pneumothoraxes due to OP. The

authors concluded that the bronchiolar lesions of polypoid

granulation observed in these cases had resolved in response

Intern Med 51: 3155-3158, 2012 DOI: 10.2169/internalmedicine.51.8319

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Table.　Case Reports of Organizing Pneumonia with Pneumothorax or Cyst

Lead author Year Age (yrs),

sex

Diagnosis Diagnosed by Cyst Pneumothorax Mechanism Steroid

therapy

Smoking

(yrs, packs/day)

Mukae H 1991 69, M COP Open lung biopsy × ◯ – ◯ –

Kofteridis DP 1999 74, M OP

(L. pneumophila)

Open lung biopsy × ◯ – × Exsmoker

(unknown)

Oguri T 1999 75, M COP TBLB × ◯ – ◯ ×

Iwanaga T 2000 46, M COP Open lung biopsy × ◯ Check-valve

mechanism, cough,

strain

× ×

Lee PC 2005 41, M COP TBLB × ◯ Cough, strain ◯ ×

Chakravorty I 2008 17, M COP Open lung biopsy × ◯ – × –

Nakayama T 1999 21, M COP TBLB ◯ × Check-valve

mechanism

× ×

Inoue T 2006 66, M COP TBLB ◯ × Check-valve

mechanism

× ×

Present case 2011 37, M OP (RA) VATS ◯ ◯ Check-valve

mechanism, cough,

etc.

◯ Exsmoker

(15,0.5)

×: absent, ◯: present, –: unknown, COP: cryptogenic organizing pneumonia, TBLB: transbronchial lung biopsy, RA: rheumatoid arthritis, VATS: video-assisted

thoracoscopic surgery

to therapy, thus facilitating airway communication and the

release of air from the cysts. Although another case thought

to be caused by the check-valve mechanism (5) was re-

ported based on the results of pathological examinations of

an open lung biopsy, the authors also did not elucidate any

specific pathological evidence. Notably, in the present case,

there were intraluminal buds of granulation tissue in the

bronchioles in close proximity to the cystic changes, which

has never been clearly demonstrated in prior reports. There-

fore, this case may support the notion that the check-valve

mechanism is responsible for the development of pneumot-

horax. Smoking may also lead to fibrosis and inelasticity of

lung tissue. Continued forceful coughing or straining may

also cause the alveolar pressure to exceed the pressure in the

interstitium of the lungs and thus trigger a rupture.

We herein presented a case of OP complicated by the sec-

ondary development of pneumothorax and cyst formation.

Notably, the presence of granulation tissue plugging the

bronchiole lumens in close proximity to the cystic changes

during the pathological examination supports the notion that

the check-valve mechanism may be a leading cause of pneu-

mothorax and cyst formation in patients with OP.

The authors state that they have no Conflict of Interest (COI).

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