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Ann Thorac Surg 2007;83:1946-1951
© 2007 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Localized Organizing Pneumonia: Report of 21 Cases

^a Department of Thoracic Surgery, San Raffaele Scientific Institute, Milan, Italy
^b Department of Respiratory Medicine, San Raffaele Scientific Institute, Milan, Italy
^c Department of Pathology, San Raffaele Scientific Institute, Milan, Italy
^d Department of Radiology, San Raffaele Scientific Institute, Milan, Italy
^e Department of Thoracic Surgery, Carlo Poma Hospital, Mantua, Italy

Accepted for publication January 29, 2007.

^_* Address correspondence to Dr Melloni, Unità Operativa di Chirurgia Toracica, Ospedale San Raffaele, Via Olgettina, 60, Milan, 20132, Italy (Email: giulio.melloni{at}hsr.it).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment References

 
Background: Thoracic surgeons have limited experience with treating localized organizing pneumonia owing to its rare occurrence in routine clinical practice.

Methods: We retrospectively investigated the clinicopathologic features of 21 patients with localized organizing pneumonia observed between 2001 and 2004.

Results: There were 15 men and 6 women. Mean age was 63 years. Eight patients (38%) were symptomatic. Computed tomographic scan showed a single lesion in 17 patients (12 nodules and 5 masses) and bilateral lesions in 4. Wedge resection was performed in 16 patients and lobectomy in 5. There was no operative mortality. Follow-up was complete in all patients (range, 2 to 46 months; median, 20 months). Surgery was curative in 15 of 17 patients with a single lesion, and no recurrence was observed (p < 0.005). The remaining 2 patients with a single lesion (2 masses) had a local relapse with the appearance of nodular lesions in the residual parenchyma. Both these patients received steroids with resolution of the lesions. All 4 patients with bilateral lesions who underwent surgery for diagnostic purposes received steroids with improvement of the radiologic aspect in 3 and stabilization of the lesions in 1.

Conclusions: Clinical and radiologic findings of localized organizing pneumonia are nonspecific, and this unusual entity is difficult to differentiate from a primary or metastatic tumor. Surgical resection allows both diagnosis and cure. However, considering the benignity of the lesion and the efficacy of steroids, major pulmonary resections should be avoided.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment References

 
Bronchiolitis obliterans organizing pneumonia (BOOP) is a well-known pathologic and clinical entity. Pathologic examination characteristically shows plugs of granulation tissue filling the lumen of the small airways and alveoli associated with interstitial inflammation [1, 2]. The classic clinical presentation (typical BOOP) is that of nonproductive cough, low-grade fever, dyspnea, and malaise [1, 3]. Although the majority of cases are idiopathic, BOOP may occur in association with a variety of diseases including bacterial infections, rheumatologic or connective tissue disorders, human immunodeficiency virus infection, organ (bone marrow, lung, and renal) transplantation, radiation and drug toxicity, and environmental exposures [1, 2]. The imaging patterns of typical BOOP have been thoroughly reported in the radiologic literature [4–6]. In the majority of cases BOOP is a diffuse lung disease with an infiltrative pattern on the chest radiograph. The most usual computed tomography (CT) appearance is of bilateral areas of air space consolidation with a patchy or predominantly subpleural distribution, often associated with ground-glass opacification and air bronchograms and/or bronchial dilatations in consolidated areas. Serial radiographs of the chest may often demonstrate the tendency of the disease to progress and change location with time [1, 2]. Pulmonary function tests in typical BOOP usually demonstrate a restrictive defect. Gas exchange abnormalities are common, and diffusing capacity of carbon monoxide is reduced in most patients. Recognition of BOOP is important because its prognosis and treatment may differ from that of other interstitial lung diseases. Although bronchoalveolar lavage coupled with transbronchial lung biopsy may be sufficient for establishing a diagnosis [7], surgical lung biopsy continues to be the gold standard. Symptoms and radiologic abnormalities of BOOP are usually responsive to steroid therapy. However, progressive disease leading to marked impairment of lung function as well as fulminating forms of BOOP have been reported in the literature [8].

When the histologic BOOP pattern presents as solitary or multiple nodules or masses, it may be termed localized organizing pneumonia. Localized organizing pneumonia, also known as focal BOOP, is a relatively rare entity. This is supported by the fact that only three major studies [9–11] with more than 10 patients appeared in the literature between 1990 and 2005. Because of its rarity, very limited data are available on localized organizing pneumonia. The precise biologic nature, natural history, and response to treatment are therefore still to be defined.

To contribute toward a better understanding of the clinical significance of localized organizing pneumonia and of the criteria for diagnoses and treatment, we retrospectively analyzed 21 patients with this unusual entity to ascertain the clinical, imaging, and evolutive features. The study was restricted to those patients who underwent pulmonary resection for nodules or masses that proved at pathologic examination to be localized organizing pneumonia. Cases of localized organizing pneumonia discovered in the surgical specimen in the vicinity of other processes after pulmonary resection performed for other reasons [12] were not considered because of their different clinical characteristics.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment References

 
This was a retrospective study, and, as individual patients were not identified, our ethics committee waived the requirement to obtain patient consent in the study. We reviewed the pathologic registries of the San Raffaele Scientific Institute, Milan, and Carlo Poma Hospital, Mantua, covering a 3-year period (August 2001 through October 2004) to identify all the patients with localized pulmonary abnormalities (nodules or masses) that had been shown to consist of BOOP at pathologic examination. Histologic specimens were reviewed again by two pathologists (G.A. and N.R.) and confirmed as localized organizing pneumonia on the basis of hematoxylin and eosin–stained sections (Fig 1). Patients’ charts were reviewed for age, sex, medical and surgical history, laboratory data at admission (including peripheral white blood cell count and C-reactive protein level), preoperative workup, type of surgical treatment, length of hospital stay, morbidity, and mortality. Computed tomographic scans of the chest were reviewed by one thoracic radiologist (R.V.). The CT features were classified as nodules (well-circumscribed lesions measuring 3 cm or less in their greatest diameter) and masses (well-circumscribed lesions measuring more than 3 cm in their greatest diameter). The following CT features were recorded for each pulmonary lesion: location, size, shape, contour, changes in the surrounding parenchyma, enlarged mediastinal lymph nodes, and pleural effusion. Follow-up data were obtained from the patients’ hospital visit. Operative mortality was defined as any death during hospitalization or within 30 days from surgery. Late mortality was defined as any subsequent death.

View larger version (161K): [in this window] [in a new window]   Fig 1. Typical pathologic features of localized organizing pneumonia with polypoid plugs of loose connective tissue protruding into the alveolar ducts and spaces. (Hematoxylin and eosin stain, magnification x100.)

	Results

Top Abstract Introduction Patients and Methods Results Comment References

 
We identified 25 patients with pathologic and radiologic evidence of localized organizing pneumonia. Four patients were excluded from the study because localized organizing pneumonia was an incidental finding occurring in the immediate vicinity of other processes (tumors, bronchiectases, and pulmonary sequestration) for which the resection had been performed. The remaining 21 patients were included in the study. There were 15 men and 6 women with a mean age of 63 years (range, 46 to 81 years). In 15 patients localized organizing pneumonia occurred in association with chronic obstructive pulmonary disease (14 patients) or Wegener’s granulomatosis (1 patient). Two patients had a prior diagnosis of neoplastic disease (1 non–small-cell lung cancer and 1 carcinoma of the urinary bladder), and localized organizing pneumonia appeared in both cases after completion of adjuvant chemotherapy. Twelve patients (57%) had a history of prior recurrent lung infections. Only 8 patients (38%) were symptomatic; symptoms included cough in 5 patients, fever in 1, chest pain in 1, and hemoptysis in 1. In the remaining 13 asymptomatic patients (62%), localized organizing pneumonia was an incidental finding on examination of chest radiographs. On admission, 1 patient had leukocytosis (>10,000/mm³), and 4 patients had high C-reactive protein levels (>6 mg/L).

Computed tomographic scan of the chest performed on all patients revealed a solitary nodule in 12 patients (Fig 2), a single mass in 5 (Fig 3), and multiple bilateral lesions (masses with nodules) in 4. The majority of the solitary nodules and masses (80%) had an irregular margin. Small nodules (satellite lesions) in the immediate vicinity of the main lesion were observed in 2 patients presenting with a solitary nodule and in 4 patients presenting with a mass. Other findings identified on CT included apical bullous emphysema in 2 patients, air bronchogram in 1, ground-glass opacifications in 2, and focal thickening of the interlobular septa in 1. No patients had enlarged (short axis > 1 cm) mediastinal lymph nodes at CT scan. The location of the lesions at CT scan was left lower lobe in 5 patients, right lower lobe in 4, right upper lobe in 3, left upper lobe in 3, medium lobe in 2, and bilateral in 4. Of the 17 solitary lesions, 12 (71%) were located in the outer third of the lung parenchyma (peripheral lesions). Fluorodeoxyglucose–positron emission tomography, performed in 3 patients (2 with a mass and 1 with a solitary nodule) to assess the stage of a presumed lung carcinoma, demonstrated intense tracer uptake in all the lesions. Pulmonary function tests, performed in all patients, revealed an obstructive ventilatory defect in 14 patients and a mixed defect in 1, although the remaining 6 were normal. Both bronchoscopy and bronchoalveolar lavage with cytologic and microbiologic analysis were negative in all patients. Transthoracic CT-guided percutaneous fine-needle aspiration biopsy performed in 9 patients was nondiagnostic or negative.

View larger version (141K): [in this window] [in a new window]   Fig 2. Computed tomographic scan of localized organizing pneumonia manifesting as a solitary nodule of the left lower lobe. This pattern may be diagnosed as primary or metastatic lung tumor.

View larger version (74K): [in this window] [in a new window]   Fig 3. Computed tomographic scans of localized organizing pneumonia manifesting as a single mass. These patterns may be diagnosed as primary lung tumors. (Left) An oval well-circumscribed mass of the left lower lobe with a satellite nodule (arrow). (Right) An oval mass of the middle lobe with a satellite area of ground-glass opacification (arrow).

The main clinical characteristics of the 21 patients in relation to the radiologic appearance of the lesions are summarized in Table 1.

	Comment

Top Abstract Introduction Patients and Methods Results Comment References

 
Although rare, localized organizing pneumonia is an extremely interesting entity for the thoracic surgeon, who may have to differentiate it from a primary or metastatic lung tumor. Described for the first time in 1989 by Cordier and colleagues [13], localized organizing pneumonia has subsequently been analyzed as a distinct form of BOOP in only a few studies [9–11, 14, 15]. Unlike typical BOOP, its clinical, radiologic, and evolutive characteristics are therefore not entirely clear.

Localized organizing pneumonia is also defined in the literature as a focal variant of BOOP, nodular BOOP, rounded BOOP, or solitary involvement of BOOP. All these terms highlight the main characteristic of this entity, namely a radiologic pattern of localized pulmonary parenchymal abnormalities. The focal involvement of the lung distinguishes this variant from the more frequent BOOP (classic or typical BOOP), a disease formally considered as interstitial pneumonia and radiologically characterized by multiple air space consolidations or interstitial infiltrations, generally with a bilateral distribution.

The exact incidence of localized organizing pneumonia is unknown, although two series report that it accounts for 13% [7] and 14% [14] of all cases of BOOP. The number of localized organizing pneumonia–related pulmonary resections is also unknown. At the San Raffaele Scientific Institute of Milan we performed 13 resections for localized organizing pneumonia (0.8%) from a total of 1,612 thoracic procedures during a 3-year period.

Typical BOOP is considered a nonspecific inflammatory process common to various injuries to the lung of either definite or idiopathic etiology [1]. Besides some drugs and radiotherapy, a further ascertained cause of BOOP is infection, especially caused by bacteria. In some patients typical BOOP is considered as a nonresolving pneumonia. It seems to be the final result of a pneumonia in which, despite infection control by antibiotics, the inflammatory process remains active with further organization of the intraalveolar fibrinous exudate that characterizes the acute stage of pneumonia [1]. Although no definitive conclusions may be drawn, it is likely that many of the cases of localized organizing pneumonia we observed were nonresolving localized lung infections. In fact, 57% of the patients in our series had a history of prior recurrent lung infections. The hypothesis of the infectious nature of localized organizing pneumonia also seems to be supported by the fact that 67% of our patients were affected by chronic obstructive pulmonary disease, which is known to present periodic pulmonary infective exacerbations and colonization by organisms such as Haemophilus influenzae and Haemophilus parainfluenzae.

The clinical characteristics of our patients were similar to those reported in other series [9–11]. Localized organizing pneumonia is usually asymptomatic or mildly symptomatic and is more frequent in male smokers with chronic obstructive pulmonary disease. The presentation of localized organizing pneumonia therefore differs considerably from that of typical BOOP, which is almost always symptomatic, not related to smoking, and characterized by a restrictive ventilatory defect [1, 2].

The CT features of localized organizing pneumonia include solitary or multiple nodules or masses with irregular margins and a round or oval shape [9, 10, 14]. In some cases associated lesions, such as satellite nodules, air bronchograms, pleural tags, or ground-glass opacifications, may be present. However, the heterogeneity of the features on CT scan and the absence of pathognomonic signs make it difficult to differentiate localized organizing pneumonia from other lung pathologic entities and in particular from primary and metastatic lung tumors [16].

All CT scans of patients in this study were reviewed by a skilled thoracic radiologist. As in other series no specific radiologic characteristics were identified, and the majority of patients underwent surgery for suspected lung carcinoma or metastases. However, it is interesting to note the high incidence of associated parenchymal lesions (50% in patients with solitary nodules and 100% in those with a mass) found in our study.

The diagnostic approach to localized organizing pneumonia varies according to the size and site of the lesion but is usually the same as that adopted for patients with suspected lung carcinoma. Peripheral nodular lesions up to 2 to 3 cm in diameter are generally removed by wedge resection with video-assisted thoracoscopic surgery technique. Video-assisted thoracoscopic surgery wedge resection is in fact a useful procedure to diagnose peripheral indeterminate pulmonary nodules [17] and is being increasingly used because of its accuracy and low morbidity. Video-assisted thoracoscopic surgery is considered to be preferable to open surgical procedures because it diminishes pain and thus the use of postoperative narcotics, preserves respiratory function, and reduces surgical trauma [17]. When wedge resection is not technically feasible, patients usually undergo a minimally invasive diagnostic workup to rule out lung cancer. However, percutaneous fine-needle aspiration biopsy providing cytologic evaluation is not useful as a histologic specimen is always necessary for a diagnosis of BOOP. Although both transbronchial lung biopsy during bronchoscopy and percutaneous tissue core biopsy are well-established procedures for the diagnosis of BOOP as they provide histologic specimens [7, 18], they are not routinely used, and some patients with localized organizing pneumonia, after a nondiagnostic or negative cytologic evaluation, directly undergo major surgery for suspected lung cancer, if functionally viable. On the other hand, the necessity to have a preoperative diagnosis in all surgical candidates remains a major controversy, and many surgeons believe that parenchymal lesions have to be resected with or without a positive diagnosis beforehand [17]. In the series reported by Oymak and associates [15], for example, 5 of 10 patients (50%) with localized organizing pneumonia underwent lobectomies or segmentectomies for diagnostic purposes. The percentage of patients who underwent lobectomy for a mass not suitable for a wedge resection in our series was 23% (5 of 21 patients). Although curative, this type of approach may be excessively invasive considering the benign nature of the disease and the efficacy of steroid treatment. It is therefore important for the thoracic surgeon to be able to clinically assess the presence of a localized organizing pneumonia to avoid unnecessary major surgery, especially in patients with reduced respiratory function.

Although no pathognomonic characteristics of localized organizing pneumonia were initially identified, in retrospect our 5 patients with a mass seem to have had distinct clinical and radiologic features. The patients were all male, and 4 of them were smokers with chronic obstructive pulmonary disease. Moreover, parenchymal lesions were oval rather than round in all 5 patients and were associated with satellite nodules (4 patients) or ground-glass opacifications (1 patient). Although these characteristics are not specific if considered individually, their coexistent presence in the same patient could suggest localized organizing pneumonia. Thus, the thoracic surgeon should be alert to the presence of a localized organizing pneumonia in patients with such clinical and radiologic characteristics accompanied by a nondiagnostic or negative fine-needle aspiration biopsy and should attempt to obtain a histologic diagnosis before performing major pulmonary resection. On the other hand, the percentage of false-negative fine-needle aspiration biopsies in patients with lung tumors greater than 3 cm in diameter is low, and tissue core biopsy has been demonstrated to be more accurate than fine-needle aspiration biopsy in specific diagnosis of benign lesions [19]. Moreover, fluorodeoxyglucose–positron emission tomography seems to be of very limited value inasmuch as it does not allow localized organizing pneumonia to be differentiated from a tumor. Localized organizing pneumonia appears, in fact, to be associated with hypermetabolism like the majority of lung tumors [20]. In our series 3 of 3 patients had positive fluorodeoxyglucose–positron emission tomography scans.

The prognosis of BOOP treated with steroids is good. The efficacy of steroids has been widely documented, and steroids continue to be recommended as the first choice of therapy for patients with symptomatic and progressive BOOP [1, 2]. Approximately 70% to 80% of patients with typical BOOP have complete clinical and radiographic resolution of their symptoms with steroid therapy [21]. Steroids have been reported to be effective not only in the treatment of typical BOOP but also in that of localized organizing pneumonia [10]. In some cases, however, both the typical form and its localized variant may not respond to treatment or may recur after therapy [1, 2, 21]. The data available in the literature on recurrent localized organizing pneumonias are, however, extremely scant.

In our experience, surgery was curative in all 12 patients with a nodule and in 3 patients with a mass. Two other patients with a mass who underwent lobectomy had a local recurrence that, however, responded well to steroid therapy. Corticosteroids were also effective in the treatment of the 4 patients with a bilateral disease, who showed an improvement of the radiologic picture in 3 patients and a stabilization of the lesion in 1. Although the limited number of patients does not allow us to draw definitive conclusions, the above data seem to indicate the usefulness of a postoperative therapy with steroids in patients with masses to prevent possible relapse of the disease.

In conclusion, localized organizing pneumonia is clinically and radiologically different from typical BOOP. Both localized organizing pneumonia manifesting as a nodule and that manifesting as a mass are difficult to differentiate from a primary or metastatic tumor. Surgical resection enables localized organizing pneumonia to be diagnosed and cured. In view of its benign nature and the efficacy of steroid therapy, every effort should be made to avoid major pulmonary resection.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Giulio Melloni Giovanni Muriana Angelo Carretta Paola Ciriaco Barbara Canneto Piero Zannini Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Melloni, G. Articles by Zannini, P. Search for Related Content PubMed PubMed Citation Articles by Melloni, G. Articles by Zannini, P. Related Collections Lung - other