Other opportunistic Infections

BACKGROUND: Lung transplant recipients routinely undergo bronchoscopy, during which bronchoalveolar lavage (BAL) fluid and transbronchial biopsies are usually obtained. These specimens are typically sent for microbiology, histopathology and cytopathology testing. Cytopathology testing is expensive, and its diagnostic value is questionable. We hypothesized that cytopathology specimens have no additional diagnostic yield beyond that of microbiology and histopathology testing in the routine care of our lung transplant patients. METHODS: We reviewed all bronchoscopies performed on a cohort of patients who underwent lung transplantation between February 1999 and August 2002 at our institution. Demographic data, immunosuppressive therapy and the incidence of opportunistic infections in this cohort of 65 patients were reviewed. To ascertain the diagnostic value of cytopathology testing, microbiology and histopathology results from bronchoalveolar lavage and transbronchial biopsy tests were compared with cytopathology results. RESULTS: Three hundred sixty-six bronchoscopies were reviewed. Microbiologic and histopathology identified 51 cytomegalovirus-, 157 fungus- and 13 mycobacteria-positive specimens as well as respiratory syncitial virus, influenza A and B, enterovirus, actinomyces, Nocardia and mycoplasma. Cytopathology of BAL fluid identified only 3 cytomegalovirus- and 13 fungus-positive specimens. The only unique diagnoses made by cytopathology were 1 case of Aspergillus and 1 unidentifiable fungal element. CONCLUSIONS: We conclude that routine cytopathology testing has little additive diagnostic value in bronchoscopic specimens from lung transplant recipients. Cytopathology results did not alter patient management in any of our 366 cases. Centers should consider discontinuing routine use of cytopathology testing of BAL fluid for surveillance or clinically indicated bronchoscopy, because the yield of this expensive test is extremely low in the setting of lung transplantation.

Disseminated nocardiosis diagnosed by fine needle aspiration biopsy: quick and accurate diagnostic approach.Diagn Cytopathol. 2006 Nov;34(11):768-71.

Nocardia is an uncommon pathogen in immunocompetent patients; however, it has been increasingly recognized as a significant opportunistic pathogen in organ transplant patients. Diagnosis of Nocardiosis is usually made by microbiologic culture or cytologic examination of pulmonary specimens including, sputum, and brushing/washings or by histologic evaluation of tissue biopsy material. We report a case of subcutaneous Nocardiosis diagnosed by Fine-needle aspiration biopsy (FNA). The patient is a 66-year-old man with a history of lung transplantation and posttransplant lymphoproliferative disorder who presented with subcutaneous masses in the right upper arm and the left shoulder. FNA was performed in an outpatient clinic setting, with immediate morphologic assessment revealing filamentous branching organisms suspicious for Nocardiosis. Subsequent examination with special stains and microbiologic culture confirmed the diagnosis. The quick and accurate diagnosis by FNA led to emergent and appropriate treatment.

Diagnosis of Pneumocystis carinii pneumonia by multiple lobe, site-directed bronchoalveolar lavage with immunofluorescent monoclonal antibody staining in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis. Am Rev Respir Dis. 1992 Oct;146(4):838-43.

The yields of both induced sputum examination and bronchoalveolar lavage (BAL) have been reported to be decreased for breakthrough episodes of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis. This study assessed whether the yield of a single middle or lower lobe BAL could be increased by the utilization of two techniques: (1) indirect immunofluorescent staining with a combination of two murine monoclonal anti-Pneumocystis antibodies in addition to routine toluidine blue O and cytopathologic staining, and (2) the performance of multiple lobe, site-directed BAL (i.e., both upper lobe and middle or lower lobe lavage, including the lobe with the greatest radiographic abnormality). Results of 252 fiberoptic bronchoscopies performed at the National Institutes of Health and the Los Angeles County-University of Southern California Medical Center were analyzed. P. carinii pneumonia was documented in 21 episodes in patients who did not receive prior anti-Pneumocystis chemoprophylaxis and in 41 episodes in patients who received aerosolized pentamidine. Monoclonal antibody staining and multiple lobe, site-directed BAL resulted in similar diagnostic yields for P. carinii in the nonprophylaxis (100%) and aerosolized pentamidine (98%) groups. If BAL had been performed without monoclonal antibody staining and multiple lobe, site-directed lavage, then the yield would have decreased to 95% in the nonprophylaxis group and to 80% in the aerosolized pentamidine group.

Pneumocystis carinii pneumonia in HIV-infected patients: diagnostic yield of induced sputum and immunofluorescent stain with monoclonal antibodies.Eur Respir J. 1992 Jun;5(6):665-9.

The purpose of this study was to evaluate the diagnostic yield of induced sputum (IS), assessing the reliability of indirect immunofluorescent stain with monoclonal antibodies (IFMoAb) and methenamine silver (Met-Ag) and analysing factors likely to influence the sensitivity of these techniques. An analysis was prospectively carried out on IS specimens collected from 61 human immunodeficiency virus (HIV)-infected patients during 69 episodes of suspected Pneumocystis carinii pneumonia. Ultrasonic nebulizers with hypertonic 2% saline were used. IFMoAb to P. carinii and Met-Ag were performed after cytocentrifugation of the specimen. Results were compared with those of bronchoalveolar lavage (BAL) with/without transbronchial biopsy (TBB), performed not more than seven days after induction of sputum. P. carinii pneumonia was confirmed in 32 episodes, of which IS was diagnostic in 23. The sensitivity of the staining procedures was 69% for IFMoAb, and 28% for Met-Ag. The three episodes of P. carinii pneumonia in patients on oral chemoprophylaxis yielded negative IS results; in contrast, IS was negative in only 6 of the 29 cases not receiving chemoprophylaxis. IS is a non-aggressive procedure that diagnosed P. carinii pneumonia in 72% of our cases. The yield increased significantly when IFMoAb was used in patients not receiving oral chemoprophylaxis.

Upper and middle lobe bronchoalveolar lavage to diagnose Pneumocystis carinii pneumonia.Am Rev Respir Dis. 1993 Dec;148(6 Pt 1):1563-6

Pneumocystis carinii pneumonia (PCP) remains the most common lethal opportunistic pulmonary infection in patients infected with the human immunodeficiency virus (HIV). Although the use of prophylactic inhaled pentamidine has effectively reduced the frequency of primary and recurrent episodes of PCP, the aerosolization of pentamidine may have altered the localization of active PCP, resulting in more upper lobe disease. The distribution of disease may have also affected the diagnostic accuracy of standard bronchoalveolar lavage of the middle lobe, with a reduction in sensitivity from about 90 to 65%. In retrospective surveys of patients from our institution, Steiger and Fahy found that pooled multiple-lobe radiographic site-directed bronchoalveolar lavage resulted in diagnostic sensitivities of 91 and 100%, respectively. We performed a follow-up prospective study of 38 consecutive patients on aerosolized pentamidine in whom we lavaged both the middle lobe and an upper lobe. We found that bilobar lavage including routine lavage of an upper lobe increases the diagnostic sensitivity of bronchoalveolar lavage alone to 95% compared with 65% if lavage is performed only in the middle lobe (p < 0.05). Radiographic studies demonstrate a concordant increase in exclusive or predominant upper lobe disease in patients on aerosolized pentamidine, but our results indicate that PCP is recovered more frequently from the upper lobe regardless of the radiographic appearance. We conclude that all patients on prophylactic inhaled pentamidine should undergo bilobar lavage with the inclusion of an upper lobe in the initial evaluation of possible PCP. The diagnostic sensitivity of 95% makes bilobar bronchoalveolar lavage an acceptable sole initial diagnostic modality without the need for initial transbronchial lung biopsy.

Blinded comparison of a direct immunofluorescent monoclonal antibody staining method and a Giemsa staining method for identification of Pneumocystis carinii in induced sputum and bronchoalveolar lavage specimens of patients infected with human immunodeficiency virus.J Clin Microbiol. 1990 Sep;28(9):2136-8.

A new direct immunofluorescence monoclonal antibody (DFA) method (Genetic Systems, Inc., Seattle, Wash.) for identification of Pneumocystis carinii in induced sputum and bronchoalveolar lavage specimens was compared in a blinded study with an established Giemsa stain method. We evaluated 148 consecutive clinical specimens from 104 patients with the following results. For the 67 patients (64%) infected with the human immunodeficiency virus (HIV), 49 were initially negative by both the DFA and the Giemsa methods, none were negative by DFA and positive by Giemsa, 6 were positive by DFA and negative by Giemsa, and 12 were positive by both methods, for a sensitivity and a negative predictive value of greater than 99%. For the six patients positive by DFA and negative by Giemsa, all were positive by both methods on evaluation of subsequently obtained clinical specimens, suggesting a specificity of greater than 99% and a false-positive rate of less than 1%. For 37 patients whose HIV status was negative or unknown, 35 were negative by both methods and 2 were positive by DFA and negative by Giemsa. The DFA method was simple to perform and required less time for scoring of stained slides than the Giemsa method, but care had to be taken to avoid false-positive readings due to extraneous fluorescence. This study indicates that the DFA method represents an advance as a sensitive, simple, and rapid way to identify P. carinii in induced sputum and bronchoalveolar lavage specimens from HIV-infected patients and suggests greater sensitivity of the DFA than the Giemsa method in this patient population.

Pulmonary aspergillosis and the importance of oxalate crystal recognition in cytology specimens. Arch Pathol Lab Med. 1986 Dec;110(12):1176-9.

A 62-year-old man, previously healthy but alcoholic, and who was clinically thought to have bacterial pneumonia, presented with a pulmonary infiltrate in the right apex, and suddenly died of exsanguinating hemoptysis. Sputum cultures yielded Aspergillus niger and Candida krusei while sputum cytology revealed numerous birefringent crystals in a background of acute inflammatory exudate. Autopsy findings showed invasive aspergillosis with a large mycetoma-containing cavity in the lung that was associated with localized massive oxalosis. This case further substantiates the fact that the presence of calcium oxalate crystals in pulmonary biopsy and cytology specimens can be regarded as an important diagnostic aid in the diagnosis of pulmonary aspergillosis due to A niger.

Diagnostic value of calcium oxalate crystals in respiratory and pleural fluid cytology. A case report.Acta Cytol. 1979 Jan-Feb;23(1):65-8.

A 56-year-old man presented with massive, left-sided pleural empyema. Sputa, pleural fluids, a bronchial washing and a bronchial biopsy revealed acute inflammatory exudate and numerous birefringent calcium oxalate crystals. One pleural fluid also showed occasional mycelia and rare conidiophores of Aspergillus niger. The fungus was abundantly cultured from all cytology specimens. Other oxalosis-related conditions were not identified in this patient. The finding of calcium oxalate crystals associated with a background of acute inflammatory cells in cellular samples of respiratory secretions and pleural fluid should be regarded as a clue to the diagnosis of infection with Aspergillus niger.