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Pulmonary nodular lesions in a 70-year-old man
European Journal of Internal Medicine 14 (2003) 332–337 www.elsevier.com / locate / ejim
Brief report
Pulmonary nodular lesions in a 70-year-old man A. Van Meerhaeghe a , *, F. Sukkarieh b , P. Cornut c , R. Peche´ a , L. Bissen b , P. Brasseur b a
´ , 6110 Montigny-le-Tilleul, Belgium Department of Internal Medicine, CHU A. Vesale, 706 route de Gozee b ´ , 6110 Montigny-le-Tilleul, Belgium Department of Radiology, CHU A. Vesale, 706 route de Gozee c Department of Anatomo-Pathology, CHU Charleroi, Charleroi, Belgium Received 8 October 2002; received in revised form 13 May 2003; accepted 13 May 2003
Abstract Bronchiolitis obliterans organizing pneumonia (BOOP) is an uncommon but increasingly recognized clinicopathologic syndrome. This report illustrates a proteiform clinical presentation of BOOP in a 70-year-old patient with cough, low-grade fever, weight loss, and hemoptysis. Chest radiograph and computed tomography (CT scan) showed nodular lesions. A video-assisted thoracoscopic procedure for biopsy of the largest nodule was performed at the end of an extensive work-up. A diagnosis of BOOP was established and, because of persistent symptomatology, corticosteroid therapy was initiated. This observation illustrates that the clinical and radiological findings of BOOP are non-specific and can sometimes mimic primary and / or secondary pulmonary malignancies. 2003 Elsevier B.V. All rights reserved. Keywords: Pulmonary nodules; Hemoptysis; BOOP; Corticosteroids
1. Introduction Bronchiolitis obliterans organizing pneumonia (BOOP), a clinicopathologic syndrome first clearly delineated by Epler et al. in 1985 [1], is a generic term for a non-specific, inflammatory lung disease simultaneously involving the terminal bronchioles and alveoli. Histological examination shows polypoid endobronchial connective tissue plugs composed of myxoid fibroblastic tissue resembling granulation tissue. This abnormal tissue extends to the peribronchiolar region, alveolar duct, and alveolar space representing the organizing pneumonic component [2,3]. Affected patients often present with a flu-like illness, respiratory symptoms, impaired pulmonary function, and diffuse patchy lung infiltrates [4]. BOOP has been described in association with pulmonary
*Corresponding author. Tel.: 132-71-921-511. E-mail address: [email protected] (A. Van Meerhaeghe). 0953-6205 / 03 / $ – see front matter 2003 Elsevier B.V. All rights reserved. doi:10.1016 / S0953-6205(03)00103-1
infections, malignancy, connective tissue disorders, organ transplantation, radiation therapy, and some medications [5]. However, idiopathic BOOP is the most common type. We describe a 70-year-old man with hemoptysis and an unusual radiological presentation of this rare disease.
2. Case report A 70-year-old Caucasian man visited his family physician because of a 6-week history of asthenia, low-grade fever (,388), non-productive cough, and 5-kg weight loss. The man was a retired policeman who had stopped smoking 8 years before (20 pack-years). He was being treated with atenolol and chlorthalidone for essential hypertension. The patient was started on antibiotics for suspected respiratory infection. Despite antibiotics, symptomatology persisted and two episodes of hemoptysis of minimal volume occurred. A chest radiograph was taken and
A. Van Meerhaeghe et al. / European Journal of Internal Medicine 14 (2003) 332–337
showed pulmonary nodules in both lungs (Fig. 1). The patient was referred to our pulmonary clinic 2 weeks later. Physical examination was normal. Results of routine blood tests were normal, except for an elevated erythrocyte sedimentation rate of 115 mm in the first hour. Arterial blood gases were normal and complete pulmonary function tests results showed a mild obstructive pattern with normal diffusion capacity. Pulmonary CT scan revealed a 3.7-cm irregular nodule in the left upper lobe with surrounding ground-glass opacities and contact with the pleura. Two other nodules were located in both lower lobes. The size of these lesions ranged from 2.0 to 2.5 cm (Fig. 2a, b). No air bronchogram was detected in any of the nodules. Primary or secondary lung malignancy was highly suspected. The patient underwent investigations to identify a primary tumor. Fiber-optic bronchoscopy and fine-needle aspiration of the left upper lung nodule under fluoroscopic vision did not demonstrate malignant cells or any infectious agent. Gastroscopy and abdominal CT scan were normal. Urologic examination and ultrasonography did not
333
reveal abnormality. Bone scintigraphy showed alterations compatible with arthrosis. Serum determination of neuronspecific enolase, carcino-embryonic antigen, and prostatic antigens were within the normal limits. After this unsuccessful work-up, a video-assisted thoracoscopic procedure was performed in order to obtain a large biopsy of the left upper lung lesion. Lung biopsy specimens showed lung tissue with scattered dark brown areas. Histologic sections (Fig. 3) showed diffuse areas of organizing loose tissue plugs (Masson’s bodies) composed of lymphocytes, macrophages, granulocytes, and fibroblasts filling bronchioli and air spaces. Numerous foamy macrophages and granulocytes were observed in the alveolar spaces. A diagnosis of BOOP was established. Because of persistence of fever and severe asthenia oral steroid therapy (prednisolone 48 mg) was started with complete resolution of symptoms and radiographic findings, except for a linear parenchymal scar in the biopsy area after 6 weeks (Fig. 2c, d). Nine months after the start of therapy and under
Fig. 1. Postero-anterior chest radiograph showing bilateral pulmonary nodules in the left upper lobe and in the lower part of the right lung.
334
A. Van Meerhaeghe et al. / European Journal of Internal Medicine 14 (2003) 332–337
Fig. 2. High-resolution CT (HRCT) (a, b) before treatment. (a) HRCT showing a left upper pulmonary nodule with irregular margin in contact with pleural surface. Ground-glass opacities are present. (b) HRCT showing two nodule-like opacities in both lower lobes. The right lesion is adjacent to the major fissure. The left nodule lies in the posterior costophrenic sulcus. (c, d) Six weeks after initiation of therapy. (c) Complete resolution of the left upper nodule. Scar parenchymal bands are visualized at former site of the lesion. (d) Disappearance of the two nodule-like opacities in both lower lobes.
treatment with 12 mg of prednisolone, the patient remains symptom-free.
3. Discussion BOOP remains idiopathic in more than 50% of cases, but specific causes and associated pathologies are now being increasingly recognized. Prevalence is comparable in both genders. BOOP is not related to smoking; in fact, most patients are non-smokers or ex-smokers. An association has been described with infectious diseases, medications, connective tissue disorders, bone marrow or organ transplantation, HIV infection, radiation therapy, myelodysplastic syndrome, and neoplasm [5]. Clinically, more than 70% of patients report cough, dyspnea, weight loss, and a prodromal flu-like illness with fever and chills. The duration of symptoms can range from
weeks to months. Crackles are heard on auscultation in two-thirds of patients [6]. There is no specific diagnostic laboratory test. The erythrocyte sedimentation rate is frequently elevated, exceeding 60 mm / h in more than 30% of patients. A moderate leukocytosis, with an increased proportion of neutrophils, may be observed [7]. Bilateral patchy alveolar infiltrates are the most common radiographic findings; however, no radiographic features are totally pathognomonic of BOOP [5]. Like those of a plain radiograph, CT scan findings are non-specific and may mimic a variety of processes. However, CT scan is more sensitive in the assessment of disease pattern and distribution of the disease than chest radiography. Pulmonary function is usually impaired, with a mild or moderate restrictive ventilatory defect being most common. Air flow obstruction may be present in smokers. In contrast to our patient, the transfer factor for carbon
A. Van Meerhaeghe et al. / European Journal of Internal Medicine 14 (2003) 332–337
335
Fig. 3. High-power magnification of typical plugs in bronchioli and in air spaces of spindle fibroblasts in light-staining matrix (Hematoxylin–Eosin staining, original magnification 3100).
monoxide is almost always reduced with mild hypoxemia at rest and / or exercise [5]. Bronchoalveolar lavage is performed to exclude other disorders, particularly infections. Video-assisted thoracoscopic lung biopsy is currently the preferred technique for diagnosing BOOP since it provides large tissue specimens that allow the diagnosis to be made with relative certainty [8]. In the present observation, the patient’s age, smoking habit, presence of hemoptysis, and radiological findings made the pre-test probability of pulmonary malignancy the highest. However, other differential diagnoses had to be considered, i.e. pulmonary metastases, primary pulmonary lymphoma, and Wegener’s granulomatosis. The most common causes of metastases seen within the lung are from adenocarcinoma of the gastrointestinal tract (30%), the genitourinary tract (30%), the breast (18%), and sarcomas (10%) [9]. Primary pulmonary lymphoma may be discovered on a routine chest radiograph. Multiple bilateral nodules, some of which may be cavitated, are one of the observed radiological patterns [10]. When present, symptoms may be
‘local’, i.e. cough, chest pain, dyspnea, and occasionally hemoptysis, and / or systemic, i.e. fever, night sweats, and weight loss. Large opacities that may be multiple and often cavitate, at times associated with hemoptysis, are common in Wegener’s granulomatosis [11]. Wegener’s granulomatosis has its peak incidence in the fourth or fifth decade of life, and the absence of involvement of the upper respiratory tract, of musculoskeletal complaints, of biological signs of kidney involvement, and of anemia, strongly lowered the pre-test probability of this disease in our patient. The above considerations prompted the diagnostic work-up developed in this case, leading to the diagnosis of BOOP. In this presentation, two main features, namely, hemoptysis and radiological pattern in BOOP, deserve further discussion. Hemoptysis is uncommon and, when it has been described, very small quantities of blood are generally expectorated. Epler et al. noted ‘slight hemoptysis’ in only 1 of 67 patients [5]. Blood-streaked sputum has been reported with idiopathic BOOP, and in one case it was associated with rheumatoid arthritis [12–14]. Hemoptysis
336
A. Van Meerhaeghe et al. / European Journal of Internal Medicine 14 (2003) 332–337
was also described in a case of influenza A-associated BOOP [15]. Cordier et al. reported hemoptysis in 3 of 16 patients [16]. Three additional cases of hemoptysis were reported in five patients in whom the presenting feature was that of a solitary lung nodule. Four of these nodules showed evidence of cavitation and three patients presented with hemoptysis [17]. For the two last cited series, the quantity of blood was not described. Severe hemoptysis as the cardinal presenting manifestation of BOOP is extremely rare and has only been reported in two cases by Mroz et al. [18]. Although the radiographic pattern of BOOP is heterogeneous and non-specific, chest radiograph and CT scan findings are sometimes characteristic. The most typical imaging profile of BOOP is that of bilateral and peripheral multiple patchy alveolar opacities. On the CT scan, the density varies from ground-glass attenuation to consolidation, and an air bronchogram may be observed in the consolidated areas. These opacities can migrate spontaneously [5]. Less frequent presentations are diffuse bilateral infiltration and solitary pulmonary nodular lesions. Radiological patterns similar to the one observed in our patient, i.e. several or multiple large (.1 cm) nodules or masses, have rarely been described [19,20]. In the study by Akira et al. [19], the number of nodules or masses varied from two to eight per case (mean five). The confusion that arises in such a situation with a lung neoplasm and / or metastasis is a real problem and large lung biopsies are necessary for diagnosis. These authors concluded that, in patients with multiple large nodular lesions or masses, BOOP should always be considered, especially when chest CT scan findings show air bronchograms, irregular margins, broad pleural tags, parenchymal bands, or subpleural lines. Chander et al. [21] reviewed the literature and observed that reports of spontaneous regression of lung metastases have recently decreased markedly. They concluded that a major reason for this observed decrease in recent years is the increasing emphasis on obtaining diagnostic tissue of multiple nodular lesions for lung metastasis, many of which have proven to be BOOP. In the Akira et al. study of patients with multiple nodular lesions, complete resolution was observed in 10 of the 12 patients without any therapy [19]. Corticosteroids are the first-line treatment for symptomatic patients and progressive disease. There is no consensus about the dosage to be used. Epler et al. recommend 1 mg / kg per day of prednisone for 1–3 months, then 40 mg / day for 3 months, and then 10–20 mg / day every day for up to 1 year. Total and permanent recovery is seen in 65–80% of treated patients. BOOP may recur, but fortunately it will respond the second time to the same dosage. The overall mortality rate is 10% [22]. Anecdotally, erythromycin has been reported to cure BOOP [1]. The anti-inflammatory properties of this antibiotic (decrease in interleukin-6 expression and decrease in
interleukin-8, and in neutrophil chemotactic activity by bronchial epithelial cells) have been cited to explain this success [23,24]. However, larger controlled studies are needed in order to exclude the role of chance, as spontaneous regressions do exist. This report illustrates that the clinical and radiological findings of BOOP are non-specific. BOOP can mimic primary or secondary pulmonary malignancy. It should be considered when large nodular lesions, with or without hemoptysis, are seen on chest radiograph or CT scan. In particular, the clinician should consider this possibility when the lesions show air bronchograms, irregular margins, and broad pleural tags. Open or video-thoracoscopic lung biopsies should be obtained in order to establish a definitive diagnosis. Corticosteroids are the mainstay of treatment in symptomatic patients.
References [1] Epler GL, Colby TV, McLoud THC et al. Bronchiolitis organizing pneumonia. New Engl J Med 1985;321:152–8. [2] Colby TV. Pathologic aspects of Bronchiolitis obliterans organizing pneumonia. Chest 1992;102(suppl):38S–43S. [3] Sulavik SB. The concept of organizing pneumonia. Chest 1989;96:967–9. [4] Bulmer SR, Lamb D, McCormack RJ, Walbaum PR. Aetiology of unresolved pneumonia. Thorax 1978;33:307–14. [5] Cordier JF. Organizing pneumonia. Thorax 2000;55:318–28. [6] Davison AG, Heard BE, MacAllister AC, Turner Warwick MEH. Cryptogenic organizing pneumonia. Q J Med 1983;207:382–94. [7] Lohr RH, Boland BJ, Douglas WW et al. Organizing pneumonia features and prognostic of cryptogenic, secondary, and focal variants. Arch Intern Med 1997;157:1323–9. [8] Deshmukh SP, Krasna MJ, McLaughlin JS. Video assisted thoracoscopic biopsy for interstitial lung disease. Int Surg 1996;81:330–2. [9] Shepherd MP. Thoracic metastases. Thorax 1982;37:366–70. [10] Weiss LM, Yousem SA, Warnke RA. Non-hodgkin’s lymphomas of the lung; a study of 19 cases emphasizing the utility of frozen section immunologic studies in differential diagnosis. Am J Surg Pathol 1985;9:480–90. [11] Fauci AS, Barton FH, Katz P, Wolff SM. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 25 years. Ann Intern Med 1983;98:76–85. [12] Alegre-Martin J, de Sevilla TF, Falco V et al. Three cases of idiopathic BOOP. Eur Respir J 1991;4:901–2. [13] Van Thiel RJ, van der Burg S, Groote AD et al. Bronchiolitis obliterans organizing pneumonia and rheumatoid arthritis. Eur Resp J 1991;4:905–11. [14] Case Records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 24-2001. A 46-year-old woman with chronic sinusitis, pulmonary nodules and hemoptysis. New Engl J Med 2002;345(6):443–9. [15] Staud R, Ramos LG. Influenza A-associated Bronchiolitis obliterans organizing pneumonia mimicking Wegener’s granulomatosis. Rheumatol Int 2001;20(3):125–8. [16] Cordier JF, Loire R, Brune J. Idiopathic Bronchiolitis obliterans organizing pneumonia: definition of characteristic clinical profile in a series of 16 patients. Chest 1989;96:999–1004. [17] Murphy J, Schnyder P, Herold C, Flower C. Bronchiolitis obliterans organizing pneumonia simulating bronchial carcinoma. Eur Radiol 1998;8:1165–9. [18] Mroz BJ, Sexauer WP, Meade A, Balsara G. Hemoptysis as the
A. Van Meerhaeghe et al. / European Journal of Internal Medicine 14 (2003) 332–337 presenting symptom in Bronchiolitis obliterans organizing pneumonia. Chest 1997;111:1175–8. [19] Akira M, Yamamoto S, Sakatani M. Bronchiolitis obliterans organizing pneumonia manifesting as multiple large nodules or masses. Am J Roentgenol 1998;170:291–5. [20] Orseck MJ, Player KC, Woollen CD, Kelley H, White PF. Bronchiolitis obliterans organizing pneumonia mimicking multiple pulmonary metastases. Am Surg 2000;66:11–3. [21] Chander K, Feldman L, Mahajan R. Spontaneous regression of lung metastasis: possible BOOP connection? Chest 1999;115:601–2.
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[22] Epler GR. Bronchiolitis obliterans organizing pneumonia. Arch Intern Med 2001;161:158–64. [23] Takizawa H, Desaki M, Ohtoshi T et al. Erythromycin suppresses IL6 expression by human bronchial epithelial cells: a potential mechanism of its anti-inflammatory action. Biochem Biophys Res Commun 1995;210:781–6. [24] Hotta M. Neutrophil chemotactic activity in COP and the response to erythromycin. Kurune Med J 1996;43:207–17.
Brief report
Pulmonary nodular lesions in a 70-year-old man A. Van Meerhaeghe a , *, F. Sukkarieh b , P. Cornut c , R. Peche´ a , L. Bissen b , P. Brasseur b a
´ , 6110 Montigny-le-Tilleul, Belgium Department of Internal Medicine, CHU A. Vesale, 706 route de Gozee b ´ , 6110 Montigny-le-Tilleul, Belgium Department of Radiology, CHU A. Vesale, 706 route de Gozee c Department of Anatomo-Pathology, CHU Charleroi, Charleroi, Belgium Received 8 October 2002; received in revised form 13 May 2003; accepted 13 May 2003
Abstract Bronchiolitis obliterans organizing pneumonia (BOOP) is an uncommon but increasingly recognized clinicopathologic syndrome. This report illustrates a proteiform clinical presentation of BOOP in a 70-year-old patient with cough, low-grade fever, weight loss, and hemoptysis. Chest radiograph and computed tomography (CT scan) showed nodular lesions. A video-assisted thoracoscopic procedure for biopsy of the largest nodule was performed at the end of an extensive work-up. A diagnosis of BOOP was established and, because of persistent symptomatology, corticosteroid therapy was initiated. This observation illustrates that the clinical and radiological findings of BOOP are non-specific and can sometimes mimic primary and / or secondary pulmonary malignancies. 2003 Elsevier B.V. All rights reserved. Keywords: Pulmonary nodules; Hemoptysis; BOOP; Corticosteroids
1. Introduction Bronchiolitis obliterans organizing pneumonia (BOOP), a clinicopathologic syndrome first clearly delineated by Epler et al. in 1985 [1], is a generic term for a non-specific, inflammatory lung disease simultaneously involving the terminal bronchioles and alveoli. Histological examination shows polypoid endobronchial connective tissue plugs composed of myxoid fibroblastic tissue resembling granulation tissue. This abnormal tissue extends to the peribronchiolar region, alveolar duct, and alveolar space representing the organizing pneumonic component [2,3]. Affected patients often present with a flu-like illness, respiratory symptoms, impaired pulmonary function, and diffuse patchy lung infiltrates [4]. BOOP has been described in association with pulmonary
*Corresponding author. Tel.: 132-71-921-511. E-mail address: [email protected] (A. Van Meerhaeghe). 0953-6205 / 03 / $ – see front matter 2003 Elsevier B.V. All rights reserved. doi:10.1016 / S0953-6205(03)00103-1
infections, malignancy, connective tissue disorders, organ transplantation, radiation therapy, and some medications [5]. However, idiopathic BOOP is the most common type. We describe a 70-year-old man with hemoptysis and an unusual radiological presentation of this rare disease.
2. Case report A 70-year-old Caucasian man visited his family physician because of a 6-week history of asthenia, low-grade fever (,388), non-productive cough, and 5-kg weight loss. The man was a retired policeman who had stopped smoking 8 years before (20 pack-years). He was being treated with atenolol and chlorthalidone for essential hypertension. The patient was started on antibiotics for suspected respiratory infection. Despite antibiotics, symptomatology persisted and two episodes of hemoptysis of minimal volume occurred. A chest radiograph was taken and
A. Van Meerhaeghe et al. / European Journal of Internal Medicine 14 (2003) 332–337
showed pulmonary nodules in both lungs (Fig. 1). The patient was referred to our pulmonary clinic 2 weeks later. Physical examination was normal. Results of routine blood tests were normal, except for an elevated erythrocyte sedimentation rate of 115 mm in the first hour. Arterial blood gases were normal and complete pulmonary function tests results showed a mild obstructive pattern with normal diffusion capacity. Pulmonary CT scan revealed a 3.7-cm irregular nodule in the left upper lobe with surrounding ground-glass opacities and contact with the pleura. Two other nodules were located in both lower lobes. The size of these lesions ranged from 2.0 to 2.5 cm (Fig. 2a, b). No air bronchogram was detected in any of the nodules. Primary or secondary lung malignancy was highly suspected. The patient underwent investigations to identify a primary tumor. Fiber-optic bronchoscopy and fine-needle aspiration of the left upper lung nodule under fluoroscopic vision did not demonstrate malignant cells or any infectious agent. Gastroscopy and abdominal CT scan were normal. Urologic examination and ultrasonography did not
333
reveal abnormality. Bone scintigraphy showed alterations compatible with arthrosis. Serum determination of neuronspecific enolase, carcino-embryonic antigen, and prostatic antigens were within the normal limits. After this unsuccessful work-up, a video-assisted thoracoscopic procedure was performed in order to obtain a large biopsy of the left upper lung lesion. Lung biopsy specimens showed lung tissue with scattered dark brown areas. Histologic sections (Fig. 3) showed diffuse areas of organizing loose tissue plugs (Masson’s bodies) composed of lymphocytes, macrophages, granulocytes, and fibroblasts filling bronchioli and air spaces. Numerous foamy macrophages and granulocytes were observed in the alveolar spaces. A diagnosis of BOOP was established. Because of persistence of fever and severe asthenia oral steroid therapy (prednisolone 48 mg) was started with complete resolution of symptoms and radiographic findings, except for a linear parenchymal scar in the biopsy area after 6 weeks (Fig. 2c, d). Nine months after the start of therapy and under
Fig. 1. Postero-anterior chest radiograph showing bilateral pulmonary nodules in the left upper lobe and in the lower part of the right lung.
334
A. Van Meerhaeghe et al. / European Journal of Internal Medicine 14 (2003) 332–337
Fig. 2. High-resolution CT (HRCT) (a, b) before treatment. (a) HRCT showing a left upper pulmonary nodule with irregular margin in contact with pleural surface. Ground-glass opacities are present. (b) HRCT showing two nodule-like opacities in both lower lobes. The right lesion is adjacent to the major fissure. The left nodule lies in the posterior costophrenic sulcus. (c, d) Six weeks after initiation of therapy. (c) Complete resolution of the left upper nodule. Scar parenchymal bands are visualized at former site of the lesion. (d) Disappearance of the two nodule-like opacities in both lower lobes.
treatment with 12 mg of prednisolone, the patient remains symptom-free.
3. Discussion BOOP remains idiopathic in more than 50% of cases, but specific causes and associated pathologies are now being increasingly recognized. Prevalence is comparable in both genders. BOOP is not related to smoking; in fact, most patients are non-smokers or ex-smokers. An association has been described with infectious diseases, medications, connective tissue disorders, bone marrow or organ transplantation, HIV infection, radiation therapy, myelodysplastic syndrome, and neoplasm [5]. Clinically, more than 70% of patients report cough, dyspnea, weight loss, and a prodromal flu-like illness with fever and chills. The duration of symptoms can range from
weeks to months. Crackles are heard on auscultation in two-thirds of patients [6]. There is no specific diagnostic laboratory test. The erythrocyte sedimentation rate is frequently elevated, exceeding 60 mm / h in more than 30% of patients. A moderate leukocytosis, with an increased proportion of neutrophils, may be observed [7]. Bilateral patchy alveolar infiltrates are the most common radiographic findings; however, no radiographic features are totally pathognomonic of BOOP [5]. Like those of a plain radiograph, CT scan findings are non-specific and may mimic a variety of processes. However, CT scan is more sensitive in the assessment of disease pattern and distribution of the disease than chest radiography. Pulmonary function is usually impaired, with a mild or moderate restrictive ventilatory defect being most common. Air flow obstruction may be present in smokers. In contrast to our patient, the transfer factor for carbon
A. Van Meerhaeghe et al. / European Journal of Internal Medicine 14 (2003) 332–337
335
Fig. 3. High-power magnification of typical plugs in bronchioli and in air spaces of spindle fibroblasts in light-staining matrix (Hematoxylin–Eosin staining, original magnification 3100).
monoxide is almost always reduced with mild hypoxemia at rest and / or exercise [5]. Bronchoalveolar lavage is performed to exclude other disorders, particularly infections. Video-assisted thoracoscopic lung biopsy is currently the preferred technique for diagnosing BOOP since it provides large tissue specimens that allow the diagnosis to be made with relative certainty [8]. In the present observation, the patient’s age, smoking habit, presence of hemoptysis, and radiological findings made the pre-test probability of pulmonary malignancy the highest. However, other differential diagnoses had to be considered, i.e. pulmonary metastases, primary pulmonary lymphoma, and Wegener’s granulomatosis. The most common causes of metastases seen within the lung are from adenocarcinoma of the gastrointestinal tract (30%), the genitourinary tract (30%), the breast (18%), and sarcomas (10%) [9]. Primary pulmonary lymphoma may be discovered on a routine chest radiograph. Multiple bilateral nodules, some of which may be cavitated, are one of the observed radiological patterns [10]. When present, symptoms may be
‘local’, i.e. cough, chest pain, dyspnea, and occasionally hemoptysis, and / or systemic, i.e. fever, night sweats, and weight loss. Large opacities that may be multiple and often cavitate, at times associated with hemoptysis, are common in Wegener’s granulomatosis [11]. Wegener’s granulomatosis has its peak incidence in the fourth or fifth decade of life, and the absence of involvement of the upper respiratory tract, of musculoskeletal complaints, of biological signs of kidney involvement, and of anemia, strongly lowered the pre-test probability of this disease in our patient. The above considerations prompted the diagnostic work-up developed in this case, leading to the diagnosis of BOOP. In this presentation, two main features, namely, hemoptysis and radiological pattern in BOOP, deserve further discussion. Hemoptysis is uncommon and, when it has been described, very small quantities of blood are generally expectorated. Epler et al. noted ‘slight hemoptysis’ in only 1 of 67 patients [5]. Blood-streaked sputum has been reported with idiopathic BOOP, and in one case it was associated with rheumatoid arthritis [12–14]. Hemoptysis
336
A. Van Meerhaeghe et al. / European Journal of Internal Medicine 14 (2003) 332–337
was also described in a case of influenza A-associated BOOP [15]. Cordier et al. reported hemoptysis in 3 of 16 patients [16]. Three additional cases of hemoptysis were reported in five patients in whom the presenting feature was that of a solitary lung nodule. Four of these nodules showed evidence of cavitation and three patients presented with hemoptysis [17]. For the two last cited series, the quantity of blood was not described. Severe hemoptysis as the cardinal presenting manifestation of BOOP is extremely rare and has only been reported in two cases by Mroz et al. [18]. Although the radiographic pattern of BOOP is heterogeneous and non-specific, chest radiograph and CT scan findings are sometimes characteristic. The most typical imaging profile of BOOP is that of bilateral and peripheral multiple patchy alveolar opacities. On the CT scan, the density varies from ground-glass attenuation to consolidation, and an air bronchogram may be observed in the consolidated areas. These opacities can migrate spontaneously [5]. Less frequent presentations are diffuse bilateral infiltration and solitary pulmonary nodular lesions. Radiological patterns similar to the one observed in our patient, i.e. several or multiple large (.1 cm) nodules or masses, have rarely been described [19,20]. In the study by Akira et al. [19], the number of nodules or masses varied from two to eight per case (mean five). The confusion that arises in such a situation with a lung neoplasm and / or metastasis is a real problem and large lung biopsies are necessary for diagnosis. These authors concluded that, in patients with multiple large nodular lesions or masses, BOOP should always be considered, especially when chest CT scan findings show air bronchograms, irregular margins, broad pleural tags, parenchymal bands, or subpleural lines. Chander et al. [21] reviewed the literature and observed that reports of spontaneous regression of lung metastases have recently decreased markedly. They concluded that a major reason for this observed decrease in recent years is the increasing emphasis on obtaining diagnostic tissue of multiple nodular lesions for lung metastasis, many of which have proven to be BOOP. In the Akira et al. study of patients with multiple nodular lesions, complete resolution was observed in 10 of the 12 patients without any therapy [19]. Corticosteroids are the first-line treatment for symptomatic patients and progressive disease. There is no consensus about the dosage to be used. Epler et al. recommend 1 mg / kg per day of prednisone for 1–3 months, then 40 mg / day for 3 months, and then 10–20 mg / day every day for up to 1 year. Total and permanent recovery is seen in 65–80% of treated patients. BOOP may recur, but fortunately it will respond the second time to the same dosage. The overall mortality rate is 10% [22]. Anecdotally, erythromycin has been reported to cure BOOP [1]. The anti-inflammatory properties of this antibiotic (decrease in interleukin-6 expression and decrease in
interleukin-8, and in neutrophil chemotactic activity by bronchial epithelial cells) have been cited to explain this success [23,24]. However, larger controlled studies are needed in order to exclude the role of chance, as spontaneous regressions do exist. This report illustrates that the clinical and radiological findings of BOOP are non-specific. BOOP can mimic primary or secondary pulmonary malignancy. It should be considered when large nodular lesions, with or without hemoptysis, are seen on chest radiograph or CT scan. In particular, the clinician should consider this possibility when the lesions show air bronchograms, irregular margins, and broad pleural tags. Open or video-thoracoscopic lung biopsies should be obtained in order to establish a definitive diagnosis. Corticosteroids are the mainstay of treatment in symptomatic patients.
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