Bronchocentric Mycosis Occurring in Transplant Recipients

doi:10.1378/chest.96.1.92

Chest

Volume 96, Issue 1, July 1989, Pages 92-95

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Although a variety of long-term, probably immunologically induced pulmonary changes have been described in recipients of both combined heart-lung and bone marrow transplantation, pulmonary infections continue to remain causes of significant morbidity and mortality as well. Herein we describe three patients (two heart-lung and one bone marrow transplant recipient) who had bronchocentric granulomatous mycosis, a tissue manifestation of fungal infection not previously described in the setting of a transplant host. Although one patient was being treated successfully with antifungal agents for his mucormycosis, two other patients eventually died of invasive aspergillosis. This emphasizes that although this process is histologically somewhat similar to bronchocentric granulomatosis, a high index of suspicion for infection needs to be maintained when this pathologic process is identified in a transplant host.

Section snippets

Case 1

This 38-year-old man underwent combined heart-lung transplantation at Stanford University Hospital in June 1983 for primary pulmonary hypertension. His clinical course was remarkably uncomplicated for nearly four years, with no episodes of cardiac or pulmonary rejection, airflow limitation, or pneumonia. He was fully rehabilitated and receiving cyclosporine A and prednisone. Forty-seven months after transplantation, the patient developed a nonproductive cough and minimal exertional dyspnea. An

Discussion

Pathologic findings in the airways, specifically bronchiolitis obliterans, have come to the foreground in combined heart-lung transplantation as being the most significant determinant of long-term survival.⁸ Now thought to be related to the process of pulmonary rejection,¹¹ such findings have been a major factor in the death of approximately 75 percent of the long-term survivors¹ and have been the stimulus for retransplantation in others (including the present case 1). Obliterative

ACKNOWLEDGMENTS

We thank Drs. Alan Glanville, Charles Lombard, and Louis Letendre for their contributions to the care of these patients, Dr. Thomas V. Colby for his helpful critical comments, Mr. Phil Verzola for his photographic expertise, and Ms. Michelle Turner for her secretarial assistance.

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Cited by (38)

High-resolution computed tomographic findings of Aspergillus infection in lung transplant patients
2014, European Journal of Radiology
Citation Excerpt :
Colonization of the airway with Aspergillus and tracheobronchial infections represent entities distinct from invasive Aspergillus pneumonia, which could occur disproportionately in lung transplant recipients and may represent the earlier stages of infection [20,21]. Thus, the respiratory tracts of lung transplant patients may be colonized by Aspergillus, which may remain non-invasive or develop into tracheobronchitis or semi-invasive or invasive aspergillosis with deterioration of the immune response [19–26]. This finding was seen in our cases, in which the predominant pattern of airway disease represented the initial insult and the infection then became invasive in some cases, represented by the coexistence of more than one pattern on HRCT findings.
The aim of this study was to assess high-resolution computed tomographic (HRCT) findings at presentation in lung transplant patients diagnosed with pulmonary Aspergillus infection.
We retrospectively reviewed HRCT findings from 23 patients diagnosed with pulmonary aspergillosis. Imaging studies were performed 2–5 days after the onset of symptoms. The patient sample comprised 12 men and 11 women aged 22–59 years (mean age, 43.6 years). All patients had dyspnea, tachypnea, and cough. Diagnoses were established with Platelia Aspergillus enzyme immunoassays for galactomannan antigen detection in bronchoalveolar lavage and recovery of symptoms, and HRCT findings after voriconazole treatment. The HRCT scans were reviewed independently by two observers who reached a consensus decision.
The main HRCT pattern, found in 65% (n = 15) of patients, was centrilobular tree-in-bud nodules associated with bronchial thickening. This pattern was described in association with areas of consolidation and ground-glass opacities in 13% (n = 3) of patients. Consolidation and ground-glass opacities were the main pattern in 22% (n = 5) of patients. The pattern of large nodules with and without the halo sign was observed in 13% (n = 3) of patients, and were associated with consolidation and ground-glass opacities in one case.
The predominant HRCT findings in lung transplant patients with pulmonary aspergillosis were bilateral bronchial wall thickening and centrilobular opacities with the tree-in-bud pattern. Ground-glass opacities and/or bilateral areas of consolidation were also common findings. Pulmonary nodules with the halo sign were found in only 13% of patients.
Rapidly progressive invasive pulmonary aspergillosis in a diabetic man
2007, Journal of Infection and Chemotherapy
A 45-year-old man was admitted to our hospital with high fever and a large amount of gray sputum. His initial chest X-ray showed broncho-bronchiolitis and thickening of the large bronchus, and he was subsequently diagnosed with pulmonary aspergillosis based on his sputum culture, polymerase chain reaction for Aspergillus fumigatus, and mannan antigen for Aspergillus. His immune responses, including neutrophil phagocytosis function and neutrophil sterilizing function, were normal as far as we could determine. He was treated with itraconazole, amphotericin B, and meropenem trihydrate, but died of respiratory failure on the twenty-fifth hospital day. Chest X-ray showed rapidly progressive invasive shadows in both lung fields, resulting in multiple cavity formation. This was a rare case of invasive pulmonary aspergillosis in a diabetic man with normal neutrophil phagocytosis function and neutrophil sterilizing function.
Aspergillus infections after lung transplantation: Clinical differences in type of transplant and implications for management
2003, Journal of Heart and Lung Transplantation
Invasive aspergillosis is a serious opportunistic infection in lung transplant recipients. It has not been fully discerned whether there are differences in the characteristics, risk factors and outcome of Aspergillus infection in single as compared with bilateral lung transplant recipients.
English-language articles identified by a Medline search through December 2000 and bibliographies were used as data sources to identify cases of Aspergillus infections in lung transplant recipients. The studies selected had to have provided a definition of invasive aspergillosis to distinguish colonization from infection.
The median incidence of Aspergillus infections in lung transplant recipients was 6.2%. In total, 58% (45 of 78) of the Aspergillus infections were tracheobronchitis or bronchial anastomotic infections, 32% (25 of 78) were invasive pulmonary, and 22% (25 of 78) were disseminated infections. Single lung transplant recipients with Aspergillus infections were significantly older (p = 0.006), more likely to have had chronic obstructive pulmonary disease as an underlying illness (p = 0.05), more likely to have developed Aspergillus infections later after transplantation (p = 0.019), and tended to have a higher incidence of invasive aspergillosis (p = 0.11) than all other lung transplant recipients. Overall mortality in lung transplant recipients with Aspergillus infections was 52%. Single lung transplant recipients (p = 0.03), and patients with late-onset infections (occurring at least 3 months after transplantation ([p = 0.045]) infections had significantly higher mortality.
Single lung transplant recipients with Aspergillus infections had an overall greater morbidity and poorer outcome than other types of lung transplant recipients. Recognition of the unique characteristics of Aspergillus infections in single lung (vs bilateral or heart–lung) transplant recipients has implications relevant for the management of lung transplant recipients with aspergillosis.
CT of noninfectious granulomatous lung disease
2001, Radiologic Clinics of North America
Citation Excerpt :
Asthmatic patients with BCG typically present at a young age (childhood to early adulthood) and invariably have underlying allergic bronchopulmonary aspergillosis.40,45 Nonasthmatic patients are usually older (mean age, 50 years) at time of presentation and may have associated conditions, such as granulomatous infections, rheumatoid arthritis, or prior organ transplantation.40,66,91 Asthmatic patients with BCG may present with symptoms of an asthma exacerbation or nonspecific complaints, such as fever, cough, chest pain, hemoptysis, anorexia, and malaise.40
Bronchocentric granulomatosis: Computed tomographic findings in five patients
2000, Clinical Radiology
AIM: The aim of this study was to assess the CT manifestations of bronchocentric granulomatosis.
SUBJECTS AND METHODS: The CT results of five patients with bronchocentric granulomatosis were retrospectively analysed. The patients ranged from 20 to 72 years of age and included three men and two women. The diagnosis of bronchocentric granulomatosis was made at lobectomy (n = 2), open lung biopsy (n = 2), and transbronchial biopsy (n = 1). Only one of the five patients had asthma.
RESULTS: The main findings consisted of a spiculated mass lesion (n = 3) or lobar consolidation with associated mild volume loss (n = 2). One of the two patients with consolidation had extensive mucoid impaction. The abnormalities involved predominantly an upper lobe in four patients and a lower lobe in one patient. In the four resected specimens, the macroscopic pathological appearance was consolidation (n = 2) and mass lesion (n = 2). Microscopically, the typical histology of airway-centred necrotizing granulomata was present in all cases. Aspergillus hyphae were identified in two cases. Nocardia sp. was cultured from the biopsy specimen in one case.
CONCLUSION: The CT manifestations of bronchocentric granulomatosis consist of a focal mass or lobar consolidation with atelectasis. These reflect the presence of granuloma formation with or without associated bronchial obstruction.Ward, S. (2000).Clinical Radiology55 , 296–300.
The histological spectrum of chronic necrotizing forms of pulmonary aspergillosis
1997, Human Pathology
Chronic necrotizing pulmonary aspergillosis (CNPA) is a rare locally destructive form of chronic aspergillosis that is recognized as a clinical syndrome, but has been poorly defined histologically. In this study, 10 cases of CNPA were evaluated from a morphological perspective. Three distinct forms of CNPA emerged. One form (n = 4) resembled a necrotizing granulomatous pneumonia centered around a central zone of infarct-like necrosis of parenchyma resulting from angioinvasive aspergillus. The second pattern (n = 4) was that of a granulomatous bronchiectatic cavity with a central fungus ball and subtle tongues of necrosis and inflammation extending into and through the fibrous wall of the cavity. A final form (n = 2) had a bronchocentric granulomatosis-like appearance with a necrotizing granulomatous bronchitis/bronchiolitis associated with luminal necrotic debris and replacement of mucosa by a palisaded histiocytic reaction. Despite the varied histomorphology, all patients survived the aspergillus infection after antifungal therapy and surgical resection. The different forms of pulmonary aspergillosis are briefly discussed, and the differential diagnosis, with particular regard to mycetomas and allergic forms of bronchocentric granulomatosis, is highlighted.

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: Manuscript received September 28; revision accepted November 4.

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Chest

Bronchocentric Mycosis Occurring in Transplant Recipients

Section snippets

Case 1

Discussion

ACKNOWLEDGMENTS

Hum Pathol

Hum Pathol

Lancet

Chest

Chest

Interstitial pneumonitis after allogeneic bone marrow transplantation: nine-year experience at a single institution.

Medicine

Lymphomatoid granulomatosis in a renal transplant recipient.

Hum Pathol

Lymphomatoid granulomatosis in a renal transplant recipient.

Aust NZ J Med