Recurrent bilateral spontaneous pneumothorax complicating chemotherapy for metastatic sarcoma.Abstract: We present the case of a 63-year-old woman with metastatic, high-grade pleomorphic pleomorphic adjective Referring to a variable appearance or morphology sarcoma who had recurrent, bilateral pneumothorax pneumothorax (nmōthôr`ăks), collapse of a lung with escape of air into the pleural cavity between the lung and the chest wall. The cause may be traumatic (e.g. while on a regimen of doxombicin and dacarbazine. We postulate that her doxorubicin-based chemotherapy induced rapid cell lysis and necrosis of peripherally located, metastatic pulmonary nodules Nodules
A small mass of tissue in the form of a protuberance or a knot that is solid and can be detected by touch.
Mentioned in: Leprosy , leading to the pneumothoraces. Other potential mechanisms include bronchopleural bronchopleural /bron·cho·pleu·ral/ (-ploor´il) pertaining to or communicating between a bronchus and the pleura or pleural cavity.
1. fistula fistula (fĭs`chlə), abnormal, usually ulcerous channellike formation between two internal organs or between an internal organ and the skin. , rupture of dilated alveoli Alveoli
Small air sacs or cavities in the lung that give the tissue a honeycomb appearance and expand its surface area for the exchange of oxygen and carbon dioxide. distal to a stenosis, chemotherapy-induced impairment of repair processes, and persistent local infection. Pneumothoraces related to pulmonary metastases tend to be refractory to conventional therapy and necessitate surgical intervention to prevent recurrences.
Key Words: bilateral pneumothorax, chemotherapy, doxorubicin, pleurodesis, pneumothorax, pulmonary metastases, sarcoma
* Pneumothorax complicates chemotherapy for metastatic sarcoma.
* The acute presentation may mimic asthma.
* Surgical or chemical pleurodesis is often necessary at initial presentation to prevent lethal recurrences.
A 63-year-old black woman had unclassified high-grade pleomorphic sarcoma involving the tibia tibia: see leg. and multiple, metastatic lung nodules (0.3-2.0 cm). Doxorubicin and dacarbazine chemotherapy was started after a left above-knee amputation amputation (ăm'pyətā`shən), removal of all or part of a limb or other body part. Although amputation has been practiced for centuries, the development of sophisticated techniques for treatment and prevention of infection has greatly . One day after starting the second cycle of chemotherapy, she came to the emergency department with a 2-hour history of acute, rapidly progressive shortness of breath Shortness of Breath Definition
Shortness of breath, or dyspnea, is a feeling of difficult or labored breathing that is out of proportion to the patient's level of physical activity. . Examination revealed diffuse expiratory ex·pi·ra·to·ry
Of, relating to, or involving the expiration of air from the lungs.
relating to or employed in the expiration of air from the lungs. wheezes with poor air exchange bilaterally. She denied any trauma. She had no history of asthma and had never smoked. Bedside chest x-ray revealed bilateral moderate-sized pneumothoraces with multiple nodules in the lung parenchyma Parenchyma
A ground tissue of plants chiefly concerned with the manufacture and storage of food. The primary functions of plants, such as photosynthesis, assimilation, respiration, storage, secretion, and excretion—those associated with living . The respiratory distress worsened, necessitating intubation intubation /in·tu·ba·tion/ (in?too-ba´shun) the insertion of a tube into a body canal or hollow organ, as into the trachea.
endotracheal intubation and mechanical ventilation within minutes of her presentation. Chest tubes inserted on both sides produced good reexpansion. She was extubated the same day, with no respiratory complaints. On hospital Day 13, she had a mechanical and talc pleurodesis with video-assisted thoracoscopy for a persistent left apical pneumothorax. She was discharged to home on hospital Day 17 and continued the chemotherapy regimen of doxorubicin and dacarbazine as an outpatient. She returned 2 months later with worsening respiratory distress. Chest x-ray film confirmed bilateral pneumothoraces, again necessitating chest tube insertions. Repeated computed tomography (CT) showed enlargement and cavitation of the previously noted lung nodules, in addition to the bilateral pneumothoraces (Figs 1 and 2). She refused further surgical intervention and was discharged to home on hospital Day 7 after apparent resolution of the pneumothorax. One week later, she was brought to the emergency room in cardiopulmonary arrest but could not be revived.
[FIGURES 1&2 OMITTED]
Cancer-related spontaneous pneumothorax is rare, accounting for 0.05% of all pneumothoraces. (1) A few of these are associated with chemotherapy or radiotherapy. We present a case of recurrent bilateral pneumothorax occurring after induction of systemic chemotherapy for high-grade sarcoma.
Spontaneous pneumothorax is classified as either primary or secondary. Primary spontaneous pneumothorax is associated with subpleural bullous bullous /bul·lous/ (bul´us) pertaining to or characterized by bullae.
Relating to or characterized by bullae. changes and occurs predominantly between the ages of 20 and 40 years. Secondary spontaneous pneumothorax occurs as a complication of intrathoracic disease. This complication typically presents after the fourth decade of life. Secondary pneumothorax may develop spontaneously with diseases such as emphysema, chronic bronchitis, pulmonary fibrosis, and malignancy. Spontaneous pneumothorax due to malignancy has been reported in patients with sarcoma, lung cancer, germ cell tumors, Hodgkin's lymphoma, and non-Hodgkin's lymphoma. (1)
Spontaneous pneumothorax usually occurs from the rupture of a subpleural apical bleb bleb (bleb) a large flaccid vesicle, usually at least 1 cm. in diameter.
A large flaccid vesicle.
a large flaccid vesicle, usually at least 0. or from cavitary pulmonary lesions. Ruptured alveoli may allow air to track into the interstitium of the bronchopulmonary bronchopulmonary /bron·cho·pul·mo·nary/ (-pool´mah-nar?e) pertaining to the bronchi and the lungs.
Relating to the bronchial tubes and the lungs. bundle and escape toward the mediastinum mediastinum /me·di·as·ti·num/ (me?de-ah-sti´num) pl. mediasti´na [L.]
1. a median septum or partition.
2. , producing a pneumomediastinum. When the air leak is sufficiently large, either a pneumothorax or subcutaneous emphysema may ensue. A rupture directly into the pleural space may lead to pneumothorax in the absence of a pneumomediastinum.
The mechanisms involving spontaneous pneumothorax associated with malignancy may be due to rupture into the pleural space of dilated alveoli distal to a stenosis, bronchopleural fistula, or associated emphysematous lung disease. (1) In some cases, the growing nodules can cause a ball valve effect, with subsequent overdistension of alveoli, leading to release of air into interstitial tissue and eventual rupture of a subpleural bleb.
Pleuroparenchymal metastases from sarcomas are a rare but classic cause of spontaneous pneumothorax, especially in children and adolescents. (2) Since the late 1970s, chemotherapy has become part of the standard of care for metastatic sarcoma. Doxorubicin, dacarbazine, and ifosfamide are the three most widely used chemotherapeutic agents in the treatment of adult soft tissue sarcomas. (3,4) In patients more than 50 years old, doxorubicin has been used as a single agent, with objective response rates of 9 to 70%. (3) To date, there have been five reported cases of bilateral secondary spontaneous pneumothorax complicating chemotherapy for metastatic sarcoma. (5-7) A majority of these patients received doxorubicin-based chemotherapy.
The suggested mechanisms for these chemotherapy-associated pneumothoraces include rapid tumor lysis and necrosis of the large metastatic pulmonary lesions, enlargement of a rapidly necrotizing necrotizing /nec·ro·tiz·ing/ (nek´ro-tiz?ing) causing necrosis.
Causing the death of a specific area of tissue. Human bites frequently cause necrotizing infections. tumor, chemotherapy-induced impairment of repair processes, and/or persistent local infection. (1,5,7) The average intervals from the initiation of chemotherapy to development of pneumothorax have been from 1 to 8 days. (1) In our patient, we postulate that doxorubicin-based chemotherapy induced rapid cell lysis and necrosis of peripherally located metastatic pulmonary nodules, leading to the pneumothoraces. The pneumothoraces were recurrent and bilateral because the metastatic nodules were multiple, bilateral, and of various sizes.
In cancer patients with radiation-associated spontaneous pneumothorax, the usual onset is 3 to 65 months from the start of radiotherapy. (1) Radiation-induced fibrosis, apical pleural Pleural
Pleural refers to the pleura or membrane that enfolds the lungs.
Mentioned in: Pneumothorax
emanating from or pertaining to the pleura. or parenchymal pa·ren·chy·ma
1. Anatomy The tissue characteristic of an organ, as distinguished from associated connective or supporting tissues.
2. injury, and focal emphysema increase the potential for formation and rupture of subpleural blebs, with the subsequent development of pneumothorax. The lung apices a·pi·ces
A plural of apex. are frequently involved, perhaps due to the increased doses of radiation targeted at the smaller thoracic diameter superiorly.
Pneumothorax complicating pulmonary metastases may be recurrent and, in this setting, lung expansion may be difficult to achieve. A persistent pneumothorax despite closed chest tube insertion should prompt a diagnosis of bronchopleural fistula, and definitive surgical intervention should be attempted. In addition, chemical pleurodesis may be considered for patients with recurrent and/or bilateral spontaneous pneumothorax related to chemotherapy. Our experience and review of literature show that surgical intervention may be appropriate in the initial presentation of bilateral pneumothorax to prevent potentially lethal recurrences.
Spontaneous pneumothorax in patients with metastatic sarcoma involving the lung can be a complication of chemotherapy. As this case illustrates, the presentation can be dramatic and may mimic status asthmaticus. A high degree of suspicion is necessary for prompt diagnosis and avoidance of unnecessary therapeutic interventions.
We thank Dr. Edward Chu for his helpful suggestions.
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of or pertaining to the mediastinum. lymphoma: A rare oncologic emergency. Ontology 1997;54: 15 18.
(2.) Spittle spit·tle
Spit; saliva. MF, Heal J, Harmer C, White WF. The association of spontaneous pneumothorax with pulmonary metastases in bone tumours of children. Clin Radiol 1968;19:400-403.
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(4.) Pinedo HM, Kenis Y. Chemotherapy of advanced soft-tissue sarcomas in adults. Cancer Treat Rev 1977;4:67-86.
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(6.) Arora R, Singh P, Aggarwal RK, Virdi HK, Singh KK, Kang HS. Bilateral spontaneous pneumothoraces in osteogenic sarcoma and extragonadal germ cell tumour. Indian J Chest Dis Allied Sci 1994;36:41-44.
(7.) Markman M, Meek AG, Wingard JR. Spontaneous pneumothorax during adjuvant chemotherapy for soft-tissue sarcoma. Johns Hopkins Med J 1981;148:264-265.
From the Department of Internal Medicine, Pulmonary Division, Yale University School of Medicine, New Haven, CT, and Bridgeport Hospital, Yale-New Haven Health, Bridgeport, CT.
Reprint requests to Anupama Upadya, MD, Department of Medical Education, Bridgeport Hospital, Yale-New Haven Health, 267 Grant Street, Bridgeport, CT 06610-0120. Email: firstname.lastname@example.org
Accepted November 26, 2001.