Histopathologic Features of Burkholderia Cepacia Pneumonia in Patients Without Cystic Fibrosis

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Histopathologic Features of Burkholderia Cepacia Pneumonia in Patients Without Cystic Fibrosis Histopathologic Features of Burkholderia Cepacia Pneumonia in Patients Without Cystic Fibrosis Deborah A. Belchis, M.D., Elizabeth Simpson, M.D., Thomas Colby, M.D. Department of Pathology, Penn State Geisinger Health System, Hershey Medical Center (DAB), Hershey, Pennsylvania; Department of Pathology, Lexington Clinic (ES), Lexington, Kentucky; and Department of Pathology, Mayo Clinic (TC), Scottsdale, Arizona Burkholderia cepacia is a ubiquitous organism that We present the histopathologic features of fatal rarely causes infection in the immunocompetent Burkholderia cepacia pneumonia in three adults host. Recently, much attention has been drawn to (one man [age 44 years] and two women [aged 40 its role as a pathogen in patients who have cystic and 43 years]). In all patients, the pulmonary infil- fibrosis (CF), in whom its isolation has been asso- trates initially were localized (right middle lobe, left ciated with rapid clinical deterioration (1–6). It is upper lobe, and right middle lobe) but rapidly pro- also gaining recognition as a pathogen in nosoco- gressed. Two open-lung biopsies and one pneumo- mial infections (7) and in patients who are immu- nectomy specimen showed necrotizing granuloma- nodeficient, particularly those who have chronic tous inflammation merging with areas of more granulomatous disease (1, 8–15). Detailed descrip- conventional necrotizing bronchopneumonia. In tions of the histopathology of B. cepacia pneumonia one patient, a mediastinal lymph node also showed are lacking. We present the histologic features stellate necrotizing granulomas. Vasculitis was ab- found in three adults who did not have CF and who sent. B. cepacia was cultured from the open-lung developed progressive pneumonia as a result of B. biopsies and bronchial wash specimens in two pa- cepacia infection. tients and from postmortem cultures of lung, sub- carinal lymph nodes, and blood in the third. The histopathology in these patients resembles that of MATERIALS AND METHODS melioidosis, which is caused by a related organism, Slides from three open-lung biopsy specimens Burkholderia pseudomallei. B. cepacia needs to be and one pneumonectomy specimen from three considered in the differential diagnosis of necrotiz- adults were received in consultation by one of us ing granulomatous inflammation. In addition, (TC). Acid-fast, Gomori’s methenamine silver, and given the rarity with which B. cepacia is identified as Brown-Brenn stains were either negative upon re- a cause of pneumonia in the immunocompetent view or reported as negative by the referring pathol- host, isolation of B. cepacia should trigger a workup ogist. Acid fast, Gomori’s methenamine silver, for underlying immunodeficiency or lead to an in- Brown-Brenn, and Warthin-Starry stains performed vestigation to exclude the possibility of a nosoco- by us on the pneumonectomy specimen from Pa- mial infection. tient 2 were also negative for organisms. The au- topsy report of Patient 1 was also reviewed. KEY WORDS: Burkholderia cepacia, Necrotizing granulomatous pneumonia. Mod Pathol 2000;13(4):369–372 RESULTS The clinical histories for each of these patients are spotty and are summarized in Table 1. All three patients were middle-aged adults (one man [age 44 years] and two women [aged 40 and 43 years]) who presented with symptoms that were consistent with Copyright © 2000 by The United States and Canadian Academy of community-acquired pneumonia. The patients Pathology, Inc. VOL. 13, NO. 4, P. 369, 2000 Printed in the U.S.A. were from different geographic regions of the Date of acceptance: August 8, 1999. United States. Patient 2 had a 15 pack-year smoking Address reprint requests to: Deborah A. Belchis, M.D., Penn State Geis- inger Health System, MC H179, 500 University Avenue, Hershey, PA history, Patient 3 did not smoke, and the smoking 17033; e-mail: [email protected]; fax: 717-531-7741. history of Patient 1 is unknown. In all three pa- 369 TABLE 1. Clinical Features Presenting Total Patient Sex Age Smoker Medical History Special Studies Chest Radiograph Outcome Symptoms Course 1 M 44 Fever N/A Pulmonary histoplasmosis, HIV negative c-ANCA Right middle lobe 9 weeks DOD age 19; chronic N/A infiltrate bronchitis; vague history of recurrent childhood infections 2 F 40 Left-sided chest Yes Pneumonia, age 34; HIV negative; normal Left upper lobe 4 months DOD pain; dyspnea, Salmonella paratyphi B sweat test; normal consolidation nonproductive pneumonia, age 35; to high cough; fever maxillary sinusitis; immunoglobulins; asthma negative ANA; c- ANCA 40(nl:0–40) 3 F 43 Frontal headache; No Lupus-like syndrome; c-ANCA N/A ANA, Ro, Right middle lobe 1 month DOD sinus discharge; migraine headaches; La antibodies infiltrate cough hypothyroidism negative N/A, not available; c-ANCA, antineutrophilic cytoplasmic antibodies; ANA, antinuclear antibodies, anti-Ro (SSA), and anti-La (SSB); DOD, dead of disease. tients, the pulmonary infiltrates initially were local- Pathologic Findings ized (right middle lobe, left upper lobe, and right The pathologic findings are summarized in Table 2. middle lobe respectively) but rapidly progressed The bronchoscopic biopsies of Patients 1 and 3 were despite treatment with broad-spectrum antibiotics. described as consistent with pneumonia. The bron- Bronchoscopic biopsies were nondiagnostic, and choscopic biopsy of Patient 2 showed hyaline mem- open-lung biopsies were performed. In Patients 2 branes, pulmonary edema, and intra-alveolar neutro- and 3, the open-lung biopsies and the bronchial phils, consistent with pneumonia. The open-lung washings/brushings grew B. cepacia. In Patient 1, biopsies and the pneumonectomy specimen were the lung tissue from the open biopsy did not yield similar and showed necrotizing granulomatous in- an organism; at autopsy, the lung, blood, and cari- flammation with prominent central neutrophilic nal lymph nodes all grew B. cepacia. karyorrhexis (Figs. 1 and 2). Microabscesses, which Patient 1’s medical history was significant for were confluent in areas, were also present. The alveoli histoplasmosis at age 19 and a vague history of were filled with fibrin exudates containing variable recurrent childhood infections. Patient 2 had a his- numbers of neutrophils and macrophages. The alve- tory of maxillary sinusitis and had been hospital- olar septa were widened by a lymphoplasmacytic in- ized twice at ages 34 and 35 for pneumonia. Salmo- filtrate. Necrosis was a prominent feature and was nella paratyphi B was identified as the cause of the extensive and confluent in some foci. The lungs were second episode of pneumonia. The patient was Af- congested, but frank hemorrhage was not present. rican American, and a hemoglobin electrophoresis Occasional small non-necrotizing granulomas were performed at that time identified the AA phenotype apparent. These were located within alveoli, and the with no evidence of hemoglobin S. Patient 3 had a larger granulomas exhibited central necrosis with 16-year history of a lupus-like syndrome and was suppuration. Non-necrotizing sarcoid-like granulo- on chloroquine at the time of her initial admission. mas and vasculitis outside the area of inflammation Serologic studies were negative for antinuclear an- were absent. The granulomatous foci merged with tibodies, anti-Ro (SSA) antibodies, and anti-La areas of more conventional bronchopneumonia (Fig. (SSB) antibodies. 3). A mediastinal lymph node removed at the time of TABLE 2. Pathologic Features Patient Transbronchial Biopsy Open-Lung Biopsy Pneumonectomy Autopsy 1 Organizing pneumoniaa Necrotizing granulomatous ND Necrotizing bronchopneumonia inflammation DADa 2 NA Acute and early organizing DAD with Necrotizing granulomatous ND intra-alveolar PMNs inflammation Mediastinal lymph node with stellate necrotizing granulomas 3 Acute pneumoniaa Necrotizing granulomatous ND ND inflammation NA, not available; ND, not done; DAD, diffuse alveolar damage. a Reported from another institution—not reviewed. 370 Modern Pathology nity to examine the histologic features in adults who do not have CF. The most striking finding was the prominent necrotizing granulomatous inflam- mation associated in some areas with extensive tis- sue necrosis. These features raised the concern of Wegener’s granulomatosis to the referring patholo- gists. The lack of vasculitis away from the area of inflammation, the absence of background multinu- cleated giant cells, and the lymph node involve- ment in Patient 2 all argued against a diagnosis of Wegener’s granulomatosis. A review of the literature reveals two reports of the histopathology of B. cepacia pneumonia. The first is an autopsy study that compared the his- FIGURE 1. Large area of geographic necrosis with adjacent necrotizing granulomatous inflammation, Patient 2 (hematoxylin & topathologic features of patients who had CF and eosin, 100ϫ). who were colonized with B. cepacia with those who were not (16). Although no histopathologic pattern was specific for any group, those who experienced a more rapid downhill course were found to have more extensive necrotizing bronchopneumonia; some showed contiguous bronchiolocentric ab- scesses. Bronchocentric cavities lined by an acute fibrinopurulent exudate, a prominent lymphoplas- macytic infiltrate, and a zone of histiocytes and multinucleated giant cells were also more prevalent in this group. Dr. Tomashefski kindly shared some of the slides from the CF study illustrating the bron- chiectasis with superimposed acute necrotizing bronchitis and bronchiolitis and bronchopneumo- nia. These
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