Idiopathic bronchocentric granulomatosis in a nonasthmatic young woman

Abstracts

Bronchocentric granulomatosis is histopathologically defined as being characterized by necrotizing granulomatous inflammation centered in the bronchi or bronchioles, which can be idiopathic or associated with infectious, immunologic or neoplastic diseases. This paper reports the case of a 26 year old nonasthmatic young woman with a 1-month history of chest pain, fever and productive cough. Chest radiography and computerized tomography were performed, and an open-lung biopsy was submitted to histological analysis. Radiographs and tomographs revealed consolidation and cavitation in the lingula. Transbronchial needle aspiration showed nonspecific inflammatory lesions, and no etiologic agent was identified. Histological examination of the specimen obtained by open-lung biopsy was consistent with idiopathic bronchocentric granulomatosis. The patient responded positively to prednisone therapy, and no relapse was documented.

Bronchocentric granulomatosis; Bronchi; Allergic bronchopulmonary aspergillosis; Prednisone

Granulomatose broncocêntrica é um achado histopatológico descritivo, caracterizado pela inflamação granulomatosa necrosante, centrada em brônquios e bronquíolos, e que ocorre associada a doenças infecciosas, imunológicas e neoplásicas, ou de forma idiopática. Este trabalho relata o caso de uma jovem não asmática de 26 anos com dor torácica, febre e tosse produtiva havia um mês, que apresentou consolidação e cavitação em segmento lingular, observadas na radiografia e na tomografia computadorizada de tórax. Punção aspirativa transbrônquica evidenciou lesão inflamatória inespecífica, sem etiologia identificada. O exame histológico de material obtido por biópsia pulmonar a céu aberto foi compatível com granulomatose broncocêntrica idiopática. Após tratamento com prednisona, houve melhora clínica, sem recidivas.

Granulomatose broncocêntrica; Brônquios; Aspergilose broncopulmonar alérgica; Prednisona

CASE REPORT

Idiopathic bronchocentric granulomatosis in a nonasthmatic young woman

José Wellington Alves dos Santos^{I (TE SBPT)}; Carlos Renato Mello^II; Gustavo Trindade Michel^III; Claudius Wladimir Cornelius de Figueiredo^IV; Jader miletho^V; Alessandro Zordan^V

^IPhD in Pneumology and Assistant Professor in the discipline of pneumology . Title of specialist by the "Sociedade Brasileira de Pneumologia e Tisiologia "

^IIFull Professor of the Pathology Department

^IIIPhD in Pneumology and Teacher of the Pneumology Discipline

^IVResident physician at the Pneumology Department

^VMedical student

^{Correspondence}

ABSTRACT

Bronchocentric granulomatosis is histopathologically defined as being characterized by necrotizing granulomatous inflammation centered in the bronchi or bronchioles and can be idiopathic or associated with infectious, immunologic or neoplastic diseases. This paper reports the case of a 26-year-old nonasthmatic young woman with a 1-month history of chest pain, fever and productive cough. Chest radiography and computerized tomography were performed, and an open-lung biopsy was submitted to histological analysis. Radiographs and tomographs revealed consolidation and cavitation in the lingula. Transbronchial needle aspiration showed nonspecific inflammatory lesions, and no etiologic agent was identified. Histological examination of the specimen obtained by open-lung biopsy was consistent with idiopathic bronchocentric granulomatosis. The patient responded positively to prednisone therapy, and no relapse was documented.

Key words: Wegener’s granulomatosis. Bronchi. Allergic bronchopulmonary aspergillosis. Prednisone, therapeutic use.

Acronyms and abbreviations used in this work

ABPA – Allergic bronchopulmonary aspergillosis

BAAR – Alcohol-acid resistant bacillus

BG – Bronchocentric granulomatosis

HE – Hematoxylin -eosin

HIV – Human immunodeficiency virus

BAL – Bronchoalveolar lavage

PCR – Polymerase chain reaction

CT – Computerized tomography

Introduction

Bronchocentric granulomatosis (BG) is a descriptive histopathological finding characterized by the granulomatous necrotizing reaction centered in the bronchi and bronchioles.^(1,2) Described in 1973 by Liebow,⁽¹⁾ it was initially related to asthmatic patients associated with allergic bronchopulmonary aspergillosis (ABPA) and to non asthmatic patients with no identified etiologic agent.⁽³⁾

Bronchocentric lesions in BG patients may present clinical, radiological and laboratory findings similar to the infectious, immunologic or neoplastic aspects of those seen in ABPA,⁽⁴⁾ tuberculosis,⁽⁵⁾ echinococcosis,^(6,7) bronchogenic carcinoma,⁽⁸⁾ glomerulonephritis,⁽⁹⁾ histoplasmosis⁽¹⁰⁾ Wegener’s granulomatosis,⁽¹⁰⁾ rheumatoid arthritis⁽¹⁰⁾ and other pathologies^(8,11,12) On the other hand, the idiopathic form^(2,3) is not related to any known etiology and an isolated histological finding, usually obtained through open-lung biopsy, should be diagnosed as BG only after careful exclusion of the other possible causes of bronchogenic granuloma.^(2,9,13,14)

We report the case a nonasthmatic patient with cavitary lesion in the lower right lobe, for which no etiology was identified.

CASE REPORT

We report here the case of a 26-year-old woman who was a nonsmoker, born and living in the city of Santa Maria, in the state of Rio Grande do Sul. She presented to our facilities with chest pain in the left hemithorax, fever, chills, night sweats, anorexia and weight loss – all over the last month. Fifteen days after the onset of these symptoms, she developed a productive cough. The patient reported no previous history of asthma, chronic respiratory infections, use of drugs or recent travels. At physical exam, her overall condition was good. She had no fever, her blood pressure was normal, and she was breathing freely. However, chest sounds included rales and cavernous breathing in the lower half of the left hemithorax and chest X-ray and CT scan showed consolidation and cavitation in the lingular segment. Blood test exhibited leukocytosis (12,170 leukocytes/mm²)with 12% rods and 2% eosinophils. Mycobacteriology of sputum samples, testing for acid-fast bacillus (AFB) and culture assays disclosed no pathogens, Parasitology of feces for eggs or larvae was negative, as was serology for human immunodeficiency virus (HIV). Levels of immunoglobulin E (IgE) were over 8.000 UI/ml, while double immunodiffusion testing for Aspergillus fumigatus, A. niger, A. flavus, Histoplasma capsulatum and Paracoccidioides brasiliensis were negative. Pulmonary function testing disclosed a moderately restrictive respiratory disorder.

Bronchoscopy showed a normal bronchial tree and the specimens obtained through bronchoalveolar lavage and bronchial brushing showed no AFB, gram-positive or gram-negative bacteria, fungi or neoplastic cells. Transbronchial fine-needle aspiration showed a nonspecific lesion. Percutaneous pulmonary fine needle aspiration disclosed absence of pus exudation, granuloma or caseous necrosis. Polymerase chain reaction (PCR) using specimens obtained through BAL was negative for Mycobacterium tuberculosis. After 20 days of administration of amoxicillin and clavulanic acid, the patient remained feverish and the radiology showed no changes. An open-lung biopsy was carried out, and the specimen obtained was stained with Verhoeff, which revealed that the bronchiole walls had been completely supplanted by necrotizing granulomatous inflammation and that histiocytes, lymphocytes, macrophages and polymorphous neutrophils surrounded the area of bronchiolar necrosis. Verhoeff staining also showed that the pulmonary artery adjacent to the impaired bronchiole presented no inflammatory reaction or tissue necrosis. This last finding allowed vasculitis to be ruled out and a diagnosis of bronchocentric granulomatosis to be made. Gomori’s methenamine silver, Brown and Brenn Gram and Ziehl-Neelsen stainings identified no fungi, bacteria or mycobacteria.

Prednisone was given in doses of 40 mg/day, achieving a good clinical response with fever cessation within the first few days. A control X-ray taken after starting the corticosteroid showed that the consolidation seen in the lingula segment was in regression. Treatment was continued for 6 months without recurrence of the disease during the two years of follow-up exams.

DISCUSSION

Bronchocentric granulomatosis, a descriptive histopathological finding, is comprised of a centralized necrotizing granulomatous reaction in the bronchi and bronchioles,^(1-3) with variable clinical and radiological manifestations.^(9,15) While fever, cough and chest pain are the most often clinical signs associated to this finding,^(3,13,15) lobe consolidation with atelectasis and solitary mass represent the main lesions found in CT scans.⁽¹⁰⁾ In addition, nodules, linear opacities, diffuse infiltrates and, eventually, pulmonary cavitation may appear.^(1-4,15) Since the case reported herein presented clinical and radiological manifestations of cavitation in the anterior subsegment of the lingular segment, combined with fever, cough and pus production, differential diagnosis was performed for various diseases such as tuberculosis, neoplasm, vasculitis and mycosis. In addition, the patient was a nonasthmatic nonsmoker and did not test positive for Aspergillus, which appears in about two-thirds of all reported cases,⁽⁸⁾ often in cases of unknown etiology^(1-3) in individuals over the age of 30.⁽⁹⁾

Since high levels of serum IgE are nonspecific, suspicion of ABPA, the primary differential diagnosis with BG, was ruled out based on clinical, radiological and laboratory data,^(4,16,17) as well as on the absence of compatible anatomical and pathological findings.

Open-lung biopsy has proven to be the method of choice in obtaining specimens appropriate for the diagnosis of BG.^(7,9,13,14) In the literature, initial analysis of samples obtained through bronchoscopy – using specific stains such as hematoxylin-eosin, Verhoeff, Brown and Brenn Gram, Ziehl-Neelsen and Gomori’s methenamine silver, in combination with appropriate culture media such as Lowenstein-Jensen and Sabouraud – has failed to identify the etiological agents responsible for BG.^(6,9,18) In the present case, due to the nonspecific inflammatory reaction seen in the specimen obtained through transbronchial fine-needle aspiration, an open-lung biopsy was performed, and the diagnosis of BG was thereby confirmed.

Treatment with corticosteroids has produced satisfactory results in patients with idiopathic BG or ABPA-related BG,^(1-3,12,13) although in cases of BG resulting from tuberculosis, echinococcosis, bronchogenic carcinoma or other pathologies, therapeutic treatments for the initial condition are employed.^(5,7,10) In the case reported here, the use of prednisone produced a good clinical and radiological response without noticeable recurrence of the disease.

We can conclude that idiopathic BG is a histopathological diagnosis of exclusion, generally made through open-lung biopsy after all known causes of bronchocentric granuloma have been excluded.^{(2, 9,13,14)}

References

Submitted for publication on March/31/03. Accepted after review on June/15/03

* Work carried out at the Hospital Universitário da Universidade Federal de Santa Maria-UFSM

• 1. Liebow AA. Pulmonary angiitis and granulomatosis. Am Rev Respir Dis 1973;108:1-18.
• 2. Ortiz-Saracho J, Vidal R, Delgado E, Fogue L, Perez-Rodriguez E. Bronchocentric granulomatosis in a nonasthmatic patient without etiologic agent. Respiration 1996;63:120-2.
• 3. Katzenstein AL, Liebow AA, Friedman PJ. Bronchocentric granulomatosis, mucoid impaction, and hypersensitivity reactions to fungi. Am Rev Respir Dis 1975;111:497-537.
• 4. Goodman DH, Sacca JD. Pulmonary cavitation, allergic aspergillosis, asthma and bronchocentric granulomatosis. Chest 1977;72:368-9.
• 5. Maguire GP, Lee M, Rosen Y, Lyons HA. Pulmonary tuberculosis and bronchocentric granulomatosis. Chest 1986;89:606-8.
• 6. Den Hertog RW, Wagenaar SS, Westermann CJ. Bronchocentric granulomatosis and pulmonary echinococcosis. Am Rev Respir Dis 1982; 126:344-7.
• 7. Hardisson D, Nistal M, Casillas M. Granulomatosis broncocéntrica associada a hidatidosis pulmonar. Arch Bronconeumol 2002;38:150-2.
• 8. Houser SL, Mark EJ. Bronchocentric granulomatosis with mucus impaction due to bronchogenic carcinoma. Arch Pathol Lab Med 2000; 124:1168-71.
• 9. Giroir BP, Squires J. Bronchocentric granulomatosis in a nonasthmatic adolescent. Pediatr Infect Dis J 1989;8:181-3.
• 10. Ward S, Heyneman LE, Flint JD, Leung AN, Kazerooni EA, Müller NL. Bronchocentric granulomatosis: computed tomographic findings in five patients. Clin Radiol 2000;55:296-300.
• 11. Myers JL. Bronchocentric granulomatosis. Disease or diagnosis? Chest 1989;96:3-4.
• 12. Millar JG, Valacer DJ, Stavola JJ, Sanan E, Di Maio MF. Idiopathic bronchocentric granulomatosis in an adolescent. Pediatr Pulmonol 1997;23:62-5.
• 13. Clee MD, Lamb D, Urbaniak SJ, Clark RA. Progressive bronchocentric granulomatosis: case report. Thorax 1982;37:947-9.
• 14. Bain GA, Flower CD. Pulmonary eosinophilia. Eur J Radiol 1996;23: 3-8.
• 15. Robinson RG, Wehunt WD, Tsou E, Koss MN, Hochholzer L. Bronchocentric granulomatosis: roentgenographic manifestations. Am Rev Respir Dis 1982;125:751-6.
• 16. Vlahakis NE, Aksamit TR. Diagnosis and treatment of allergic bronchopulmonary aspergillosis. Mayo Clin Proc 2001;76:930-8.
• 17. Sharma OP. Diagnosing pulmonary infiltration with eosinophilia syndrome, part 1. J Respir Dis 2002;23:411-20.
• 18. Mourad WA, Vallieres E, Power RF, Hirji M. Fine-needle aspiration cytology of bronchocentric granulomatosis: a potential diagnostic pitfall. Diagn Cytopathol 1996;14:263-7.

Publication Dates

• Publication in this collection
  12 May 2004
• Date of issue
  Dec 2003

History

• Accepted
  15 June 2003
• Received
  31 Mar 2003