Nocardia cyriacigeorgica intracavitary lung colonization: first report of an actinomycetic rather than fungal ball in bronchiectasis

Abstract

We report the first case of an isolated endobronchial mass caused by Nocardia cyriacigeorgica in an immunocompetent patient with a history of lung surgery; this is a rare presentation of an emerging opportunistic pathogen. The infection was successfully eradicated by surgery. Microbiologists and clinicians should pay more attention to this group of filamentous bacteria, which in the past have often been neglected by medical personnel.

Background

Nocardia is a strictly aerobic, soil-borne, typically filamentous, Gram-positive, weakly acid-fast actinomycete. It is ubiquitous and the classic route of infection is via the respiratory tract (ie, by inhalation). Nocardia present in the sputum is not considered a contaminant; rather, it may be representative of colonisation, a subclinical condition if accompanied by a normal chest roentgenogram or active pulmonary infection.¹ Nevertheless, a positive sputum culture in the presence of symptoms and signs of pulmonary infection is sufficient evidence of nocardiosis to initiate treatment, especially in patients who may have an altered immune status and underlying conditions. Bronchiectasis is the most frequent underlying pathology associated with colonisation by Nocardia^2–6 and in a recent study Nocardia cyriacigeorgica was identified as the most frequently detected species in patients thus afflicted.^{3 4} To the best of our knowledge, this is the first description of a patient with bronchiectasis associated with actinomycetic colonisation and mass formation involving N cyriacigeorgica.

We decided to study this case:

• To report the first case of an actinomycetic ball in bronchiectasis.

• To highlight the fact that not every solid mass within a lung cavity is a fungus ball (aspergilloma).

• To underline the fact that Methenamine Silver staining reveals more filaments than any other staining method.

Case presentation

The patient, a 77-year-old housewife, presented at our emergency room with haemoptysis and was admitted. Physical examination revealed a healed thoracic surgical scar on her right side and digital clubbing. Her blood pressure was 130/80 mmHg; pulse rate, 80/min; respiration rate, 20/min and temperature, 36°C. She had a long history of chronic obstructive pulmonary disease with respiratory and systemic symptoms including a productive cough, low-grade intermittent fever and malaise.

Her medical history revealed that she had undergone lung surgery 43 years ago. A right lower lobe lobectomy was performed and the subsequent pathological examination indicated bronchiectasis.

Postoperatively, she presented with a productive cough on several occasions, and after 2 weeks her respiratory symptoms became pronounced. She began experiencing repeated haemoptysis. A high-resolution axial CT scan revealed a cavitary lung lesion in the lingula that resembled a fungus ball and was filled with opacity (figure 1). Resection of the lingula was performed, and a section of the lingular segment showed bronchiectasis, a thin-walled cavity partially filled with inflammatory debris and a ball of granular dark-brown material. The intracavitary specimen comprised numerous Gram-positive branching filaments, but only N cyriacigeorgica was cultured. Microscopically, the bronchiectatic lesion and the cavity were covered by mucosa; metaplasia and ulceration were apparent. Grocott Methenamine Silver staining of a section of the ball revealed zonation growth of thin-branched actinomycetic filaments (figure 2). The postoperative course was uneventful.

Figure 1.

(A) Chest x-ray shows heterogeneous pulmonary opacity in lower left lung. (B) High resolution axial CT scan shows cavitary lung lesion in lingula filled by opacity resembling a fungus ball. (C) CT shows a pulmonary bronchiectasis in the lingula (arrow).

Figure 2.

Nocardia cyriacigeorgica. Actinomycetic ball from the cavity of the pulmonary lingular lobe. (A) Cut section of the ball showing zonation of actinomycete filaments growth. (B) Section of the ball showing thin branched filaments (GMS-stained, ×40 and ×1000, respectively).

Investigations

Microbiology

Gram staining of the ball revealed numerous Gram-positive branching filaments, and modified Ziehl-Neelsen staining (Kinyoun) revealed Gram-positive, weakly acid-fast, branching filamentous rods consistent with Nocardia. The specimen was also inoculated onto Sabouraud dextrose agar (25°C) and Brain Heart Infusion agar (35°C). White colonies consistent with Nocardia-like organisms appeared on all media after 3–15 days of incubation.

Sequence analysis

DNA sequencing was performed with an automatic sequence analyser (Applied Biosystems USA) using a dye terminator cycle sequencing kit (PE Applied Biosystems) and the sequencing primer 515FLP, which revealed 100% homology with several sequences of N cyriacigeorgica.

Differential diagnosis

• Pulmonary fungus ball (aspergilloma)

• Pulmonary encapsulated abscess cavity

• Sequestrum of non-viable pulmonary tissue

• Cavitary lung carcinoma

• Pulmonary actinomycosis

Discussion

Fungus balls are commonly formed after infection with Aspergillus spp. However, other species of true fungi may also produce a fungus ball. Rarely, true bacteria such as those in the Actinomyces^{7 8} and Nocardia^{9 10} genera may form a movable mass of actinomycetes. Upon gross examination these may greatly resemble a fungus ball, but histopathological examination will reveal thin, branching filaments and the lack of true hyphae. For this reason, the term ‘fungus ball’ should not always be applied to intracavitary bacterial filaments.^{9 11}

Nocardia spp. are becoming more frequently recognised as serious but potentially treatable pathogens. The most frequently detected pathogens involved in human infections are members of the Nocardia asteroides complex.¹² In 2001, Yassin et al first described N cyriacigeorgica (formerly N cyriacigeorgici) in bronchial secretions of a patient with chronic bronchitis.^{12 13} At present, N cyriacigeorgica is considered an emerging pathogen that requires closer attention and microbiology laboratories need to adapt laboratory protocols for its specific identification.^{14 15}

Learning points.

This case reveals the following important points:

• A cavitary lung lesion with opacity in a patient with a history of bronchiectasis and haemoptysis is not synonymous with an aspergilloma (fungal ball).

• Clinicians and radiologists should be aware of this unusual manifestation of nocardiosis.

• The findings on thoracic CT contributed to early consideration of intracavitary lung colonisation in the differential diagnosis.

• The term ‘fungus ball’ should not be applied to an intracavitary mass comprising actinomycete filaments.