Kurume Medical Journal, 50,147-150, 2003Case Report

Rapid-growth Lung Cancer Associated with a Pulmonary

Giant Bulla: A Case Report

HISASHI NAKAMURA, SHINZO TAKAMORI, KEISUKE MIWA, MART FUKUNAGA,

KANETAKA MAESHIRO, TOSHIHIRO MATSUO, AKIHIRO HAYASHI

AND KAZUO SHIROUZU

Department of Surgery, Kurume University School of Medicine,

Kurume 830-0011, Japan

Summary: A giant bulla of the lung is suggested as a risk factor for lung cancer. Here we report a

case with lung cancer in a giant bulla, which showed rapid progression. A 57-year-old man, who

had a history of heavy smoking, was admitted to our hospital due to hemoptysis. A chest X-ray

revealed a giant bulla with a ground glass shadow and a high fluid level in the right upper lung.

Sputum cytology was negative for malignant cells. A chest X-ray a month later showed increases of

the size of the radio-opaque shadow and of the air-fluid retention, suggesting pulmonary hemor-

rhage from the giant bulla. Limited resection or lobectomy was indicated, but pneumonectomy was

performed due to the severe air-leak. Macroscopically, a multiple nodular tumor arose from the bulla wall, which might be related to blood flow and necrotic tissue. The postoperative pathological

diagnosis was papillary adenocarcinoma. Unfortunately, the patient developed a recurrence of

carcinoma in the pleuroperitoneal cavity and died at 2.5 months after the operation.

Based on this report and review of other cases in the literature, we should keep in mind the

rapid progression of lung cancer in association with an emphysematous bulla.

Key words giant bulla, lung cancer

INTRODUCTION

The incidence of lung cancer in bullous disease occurs with significant frequency among the general population, and its prognosis is frequently poor. Stoloff et al. [1] reported that the frequency of lung cancer in subjects with bullous disease was approxi-mately 32 times higher than in those without this abnormality. In this report, we describe a patient with lung cancer associated with a giant bulla, who presented a progressive course after the operation.

CASE REPORT

A 57-year-old Japanese man, presented hemopty-sis on 1 1 April, 2002. A chest X-ray showed a giant bulla accompanied with a ground glass shadow and fluid retention in the right upper lung (Fig. 1).

Sputum cytology was negative for malignant cells. Hemoptysis continued for the next month, and a chest X-ray a month later showed increases of the area of radio-opaque lung and of the air-fluid reten-tion (Fig. 2), which suggested pulmonary hemor-rhage from the giant bulla. The patient was admitted to our hospital for further examination and treatment

on 8 May, 2002. The patient had a history of heavy smoking (Brinkmann Index 1110), and the past his-tory included pneumonia and pneumothorax in the right lung. On admission, the patient suffered hemoptysis, chest pain, and dyspnea. The circulatory and digestive systems had no abnormal signs, but a weak coarse crackle sound was heard over the right chest wall. A bronchofiberoptic examination and pul-monary function tests could not be performed. A chest computed tomography scan showed a ground

glass shadow and fluid retention, with appearance of

Received for publication May 19, 2003

Reprint requests to: Dr. Hisashi Nakamura, Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. Tel: +81-942-31-7566 Fax: +81-942-34-0709

148 NAKAMURA ET AL.

a nodular shadow in the right upper lobe of the lung

(Fig. 3). No other tumor was detected in the brain, liver, or bone. First, we attempted to stop the bleed-

Fig. 1. Chest X-ray showing ground glass shad-

ow and fluid retention in the giant bulla in the right

lung.

Fig. 2. Chest X-ray showing increase in the

radio-opaque lung and air-fluid retention in the

giant bulla in the right lung.

Fig. 3. Chest CT scan showing the appearance

of a nodular shadow in the giant bulla in the right

lung.

Fig. 4. Macrospically, a multiple nodular tumor

arose from the bulla wall, which might be related to

blood and necrotic tissue.

ing using the bronchial artery embolism, but a 4th

intercostal artery angiographic examination showed a

shunt from the intercostal artery to the superior pul-

monary vein. Thus, it was impossible to perform the

bronchial artery embolism. Therefore, the patient

was transferred to the department of surgery for an

emergency operation. Preoperative diagnosis was

pulmonary hemorrhage from the giant bulla or

malignant tumor, and thoracotomy was performed on

14 May, 2002. Limited resection or lobectomy was

indicated, but right pneumonectomy was performed

due to severe air-leak. Subsequently, regional lym-

phnode dissection was performed. Macroscopically,

the markedly emphysematous right upper and lower

lobes contained several bullae varing in size. The

yellowish multiple nodular tumor with a base of

9.5•~6.0 cm arose from the giant bulla wall, which

Ku rume Medical Journal Vol. 50, No. 3, 4, 2003

LUNG CANCER 149

Fig. 5. Histological findings of the surgical spec-

imen showing moderately differentiated papillary

adenocarcinoma with extensive necrotic tissue. (HE,

•~ 20)

might be related to the blood flow patterns and necrotic tissues (Fig. 4). Microscopically, the tumor was a moderately differentiated papillary adenocar-cinoma with extensive necrotic tissue (Fig. 5). The wall of the giant bulla was thickened by connective tissue proliferation, and carcinoma cells were found on the bulla wall. The parenchymal tissue around the bulla wall was emphysematous, and fibrous changes were detected. The hilar and mediastinal lymph nodes were negative for tumor cells. The patient developed a recurrence in the pleuroperitoneal cavity and died at 2.5 months after the operation due to cancer progression.

DISCUSSION

Lung cancer develops more frequent in cases with a bullous disease such as emphysematous giant bulla [2] or lung cyst [3]. Cases of a carcinoma aris-ing in bullous lung disease have been reported during the past 40 years [2,4-8], and the incidence of lung cancer associated with bullous emphysema has been estimated to be 2-6% of the general population [8].

Goldstein et al. reported the frequency of a

pulmonary bulla in patients with lung cancer. They demonstrated a giant bulla in 18 patients among 411

patients with primary lung cancer. The frequency of a giant bulla in cases with lung cancer was approxi-mately 6 times higher than in those without lung cancer. The histological types were anaplastic cancer in 12, squamous cell carcinoma in 4, and adenocar-cinoma in 2. All cases were male smokers in the age range of 40-59 years [2]. Stoloff et al. analyzed

75,000 chest X-rays and reported that cancer was found in 6.1 % of patients with bullous disease, and in only 0.16% of patients without bullous disease. The frequency of lung cancer in cases with bullous disease was approximately 32 times higher than in those without bullous disease. They also included data from a retrospective study, and found 26 addi-tional cases of lung cancer with bullous disease in the lung. The tumors were considered to have origi-nated inside the bulla in 6 of these cases, and the bulla and tumors were separated by normal lung parenchyma in the remaining 20 cases [1].

Although the carcinogenesis of bullous disease remains uncertain, various etiologies have been pro-posed for the association between bullous disease and lung cancer. The wall of a bulla may undergo metaplastic transformation [9] or be related to scar [10]. Stagnation of carcinogens in the bulla may induce carcinogenesis [11] or inhibit antielastase enzymes, resulting in interalveolar-septal destruction with subsequent bulla formation [12].

The clinical features of lung cancer associated with giant bullous disease were reviewed in 67 reported patients with definitive histological diagno-sis, including our patient. We found that the charac-teristics of a patient with lung cancer and coexistent giant bulla were: 1) most are male smokers of age over 50 years (average, 54.9), 2) main subjective symptoms are hemosputum (27.2%), fever (23.4%), and asymptom (19.1%), 3) the histological types are various, adenocarcinoma (47.8%), large cell carcino-ma (28.3%), and squamous cell carcinoma (20.9%), 4) no preoperative diagnosis (29.8%), and opera-tively or postoperatively definitive diagnosis (70.2%) and 5) rapid growth in the giant bulla, and poor prognosis. Our patient was a 57-year-old male smoker. A heavy smoking habit has been discussed as a cause of lung cancer in patients with a coexistent giant bulla. The hemoptysis due to pulmonary hem-orrhage from the giant bulla was an unusual symp-tom. His lung cancer showing rapid growth from the giant bulla during one month was a special feature and difficult to diagnose preoperatively. Radiological diagnosis may be difficult when the tumor is small and appears as an excrescence on the wall of the bulla, especially in the case that an air-fluid level obscures the tumor. The histological diagnosis of lung cancer in this case was a moderately differ-entiated papillary adenocarcinoma, and the carcino-ma cells were found on the bulla wall. The majority of lung cancers associated with bullous,disease are non-small cell cancer, and there has been only one

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150 NAKAMURA ET AL.

report of bullous disease associated with small-cell lung cancer [7].

In conclusion, we should keep in mind the

potential for rapid growth in lung cancer in a patient with a giant bulla. Regular follow-up must be con-ducted to detect any early small lung cancer in

patients with a giant bulla in the lung.

REFERENCES

1. Stoloff IL, Kanofsky P, and Magilner L. The risk of lung

cancer in males with bullous disase of the lung. Arch

Environ Health 1971; 22:163-167.

2. Goldstein MJ, Snider GL, Liberson M, and Poske RM.

Bronchogenic carcinoma and giant bullous disease. Am

Rev Respir Dis 1968; 97:1062-1070.

3. Svenneving JL, Bugge-Asperheim B, and Boye NP.

Carcinoma arising in a lung cyst. Scand J Thor

Cardiovasc Surg 1979;13:153-155.

4. Korol E. The correlation of carcinoma and congenital

cystics emphysema of the lungs: report of ten cases. Dis

Chest 1953; 23:403-411.

5. Ettman EK. Bullous disease of the lung and bron-

chogenic carcinoma. South Med J 1968; 61:743-747.

6. Scannel JG. 'Bleb' carcinoma of the lung. J Thorac

Cardiovasc Surg 1980; 80:904-908.

7. Aronberg DJ, Sagel SS, LeFrak S, and Kuhn C. Lung

carcinoma associated with bullous lung disease in young

men. AJR 1980;134:249-252.

8. Watts MA, Klayton RJ, and Munzel TL. Bullous emphy-

sema and carcinoma of the lung: case report. Mil Med

1982;147:320-323.

9. Womack NA, and Graham EA. Epithelial metaplasia in

congenttal cystic disease of the lung: its possible relation

to carcinoma of the bronchus. Am J Pathol 1941; 17:531-

537.

10. Yokoo H, and Suckow EE. Peripheral lung cancers aris-

ing in scars. Cancer 1961; 14:1205-1215.

11. Miyata Y, Ishihara T, Omiya T, and Tamaki S. A case of

bilateral giant emphysematous bullae with lung cancer.

Jpn J Thorac Surg 1981; 34:392-394.

12. Ogawa D, Shiota Y, Marukawa M, and Hiyama J. Lung

cancer associated with pulmonary bulla: case report.

Respiration 1999; 66:555-558.

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