Abstract
Background: The objective of this study was to clarify the clinical features of pulmonary cryptococcosis using chest computed tomography (CT) and positron emission tomography with [18F]fluoro-2-deoxy-d-glucose (FDG-PET), with a view to developing appropriate treatment. Methods: We analyzed the clinical features, and chest CT and FDG-PET characteristics of six cases of pulmonary cryptococcosis that were treated by surgery. The patients comprised four males and two females, ranging in age from 28 to 79 years. Results: All the patients were asymptomatic and had no extrapulmonary involvement. In all cases, chest CT showed nodular shadows. Spiculation and convergence of peripheral vessels were demonstrated in three cases, and pleural indentation in two cases. FDG-PET was performed in four of the cases, and showed accumulation of FDG in all of them. The standard uptake value (SUV) ranged from 0.93 to 4.85. Chest CT findings and accumulation of FDG made it difficult to distinguish pulmonary cryptococcosis from malignancies. Segmentectomy or wedge resection was performed in all cases for pathological diagnosis, and this revealed Cryptococcus fungal bodies. After surgical resection, no sign of relapse has been seen in any of the patients. Conclusions: Surgical resection is recommended for both diagnosis and treatment of pulmonary cryptococcosis.
1 Introduction
Pulmonary cryptococcosis is caused by inhalation of Cryptococcus neoformans. It is well known that pulmonary cryptococcal infections tend to occur in immunocompromised individuals, although they can sometimes occur even in immunocompetent hosts [1–3]. As more individuals are undergoing regular medical examinations, the number of cases of cryptococcosis detected incidentally is increasing.
There have been several reports describing the clinical and radiographic features of pulmonary cryptococcosis [1–3]. Chest computed tomography (CT) frequently shows solitary or multiple nodular shadows, or occasionally cavitation [1,2]. Also, positron emission tomography using [18F]fluoro-2-deoxy-d-glucose (FDG-PET) sometimes demonstrates accumulation in pulmonary cryptococcosis [4]. These features make it difficult to distinguish pulmonary cryptococcosis from lung cancer or tuberculosis. In the present study, we retrospectively analyzed the clinical features, chest CT findings, and accumulation of FDG in six cases of pulmonary cryptococcosis treated by surgery over the last 4 years.
2 Materials and methods
The six patients with pulmonary cryptococcosis underwent surgery between August 2000 and September 2004. They comprised four males and two females, and ranged in age from 28 to 79 years. Chest CT was performed in all six cases, and FDG-PET was performed in four of the six patients from June 2002 onward. The corrected PET images were evaluated qualitatively by visual inspection and semi-quantitatively by analysis of standard uptake value (SUV).
3 Results
All of the patients were asymptomatic at the time of admission, and had no extrapulmonary involvement. No progressive dissemination occurred during the follow-up period. In two cases an abnormal shadow was detected by chest X-ray during routine medical examinations, and in four cases the lesion was revealed by chest CT during medical examinations for other diseases. Serum cryptococcal antigen was examined in two of the six cases, but was undetectable.
Details of chest CT findings and SUV in these cases are shown in Table 1 . In all cases, chest CT showed a single nodular shadow less than 20 mm in diameter. Three cases showed an irregular margin, spiculation and convergence of peripheral vessels, and two of these cases showed pleural indentation (Fig. 1a ). In the other three cases, nodular shadows with a regular margin were observed (Fig. 1b), and cavitation was observed in one case. There was no evidence of satellite lesions, lymph node swelling, or pleural effusion in any of the six patients. FDG-PET showed accumulation of FDG (SUV, 0.93–4.85) in all four patients who underwent this examination.
Analysis of chest CT findings and SUV of FDG-PET in the six cases of pulmonary cryptococcosis
Analysis of chest CT findings and SUV of FDG-PET in the six cases of pulmonary cryptococcosis
Chest CT shows a single nodular shadow with an irregular margin, spiculation, convergence of peripheral vessels and pleural indentation (a) or a regular margin (b) (arrows indicate the nodular shadow).
Chest CT shows a single nodular shadow with an irregular margin, spiculation, convergence of peripheral vessels and pleural indentation (a) or a regular margin (b) (arrows indicate the nodular shadow).
Only one case was diagnosed as pulmonary cryptococcosis by CT-guided needle aspiration before surgery. The other cases were not diagnosed before surgery because of technical difficulty with transbronchial biopsy and CT-guided needle aspiration. In two cases, segmentectomy, and in four cases, wedge resection were performed for both diagnosis and treatment. All the patients were administered 200 mg/day fluconazole orally after surgery, five for 1 or 2 months, and one for an unknown period. Since discontinuation of fluconazole, no sign of relapse has been seen.
4 Discussion
Pulmonary cryptococcosis caused by inhalation of C. neoformans is an infectious fungal disease that occurs frequently in immunocompromised hosts. However, there have been several reports of pulmonary cryptococcosis occurring in healthy individuals [1–3]. Kishi et al. [1] reported the clinical features, CT findings and treatment of 22 cases of pulmonary cryptococcosis, and stated that approximately 90% of the cases were asymptomatic and detected incidentally on chest radiographs taken for mass health screening or routine follow-up of other diseases. Similarly, in our series, all the patients were asymptomatic and their lesions were discovered incidentally by radiography. The test for serum cryptococcal antigen has high sensitivity and specificity, and measurement of cryptococcal antigen in serum can also provide a means of assessing the response to antifungal therapy [5]. However, in our series, serum cryptococcal antigen was undetectable in the two patients who were tested.
The characteristics of chest CT findings in pulmonary cryptococcosis have been well documented. It has been reported that chest CT shows a single nodular shadow in 50–60% of patients with pulmonary cryptococcosis, spiculation in 30%, and convergence of peripheral vessels and pleural indentation in 50% [1,2]. All the cases in our series had a single nodular shadow, 50% showed spiculation and convergence of peripheral vessels, and 33% showed pleural indentation. Such a single nodular shadow makes it difficult to distinguish pulmonary cryptococcosis from lung cancer or tuberculosis [6]. Moreover, spiculation, convergence of peripheral vessels, and pleural indentation on chest CT make distinction from adenocarcinoma difficult [7]. Several groups have reported that the incidence of cavitation in pulmonary cryptococcosis varies from 0 to 30% [1–3]. Cases that show cavitation need to be discriminated from squamous cell carcinoma or pulmonary tuberculosis. In our series, cavitation was detected in only one case (17%).
FDG-PET is a relatively new imaging modality that facilitates distinction between benign and malignant lesions, especially for single nodules [8,9]. However, FDG-PET sometimes shows accumulation in inflammatory and granulomatous conditions such as pulmonary cryptococcosis [4]. FDG accumulates in macrophages and young granulation tissue caused by pulmonary cryptococcosis [10]. There have been few reports of FDG-PET analysis of pulmonary cryptococcosis, except for one case report by Hsu et al. [4]. In the present series, FDG-PET showed accumulation of FDG in all four cases that were examined by this modality, and these cases were difficult to distinguish from lung cancer.
In our series, we found that the radiographic features and FDG uptake of pulmonary cryptococcosis sometimes resembled those of lung cancer. Therefore, we considered that surgical resection would be the optimal treatment, particularly in cases where the diagnosis has not been confirmed preoperatively, as it allows both diagnosis and treatment to be performed concurrently.
The treatment of pulmonary cryptococcosis in immunocompetent hosts is controversial. Many reports have indicated that the infection can be cured by administration of antifungal drugs alone. However, Kishi et al. [1] reported eight cases that were treated by surgical resection alone, and none showed relapse thereafter. Therefore, we recommend surgical resection if the nodular shadow of preoperatively diagnosed pulmonary cryptococcosis is single and the lesion can be excised. In our series also, none of the cases showed relapse after surgical resection.
