The clinical and radiological characteristics of pulmonary cryptococcosis in immunocompetent and immunocompromised patients

We retrospectively reviewed the medical records and radiological profiles of patients diagnosed with PC who received surgical resection in our center between May 2015 and November 2020. Patients with PC would be included in the study if they met all of the following conditions: 1. presence of pulmonary nodule or mass in which lung cancer could not be ruled out clinically; 2. PC was histologically and microbiologically confirmed; 3. clinical data and CT imaging information were available.

The following clinical data were extracted from the medical records: sex, age, presenting symptoms, cormorbidities, smoking status, surgical and antifungal therapy, pathology, follow-up, and prognostic outcomes. Chest CT images were analyzed and the location, pattern, size, margins, pleural sign, and presence of air bronchogram, cavitation, Halo sign, and mediastinal lymphoadenopathy were recorded. Positron emission tomography (PET)/CT images were evaluated for standardized uptake values (SUVs) if accessible. Pulmonary Lesions or lymph nodes with higher FDG uptake was defined when their maximum SUV (SUV_max) was higher than that in the normal lung tissues or the mediastinal blood pool, respectively. Diagnosis of PC was confirmed by postoperative pathology. All samples were formalin-fixed, paraffin-embedded, and stained with haematoxylin–eosin (H&E), Gomori methenamine silver (GMS), and periodic acid-Schiff (PAS). The Institutional Review Boards of Second Xiangya Hospital approved the study.

Descriptive analyses of patient demographics, clinical features, radiological findings, pathological data, and treatment outcomes were performed. All data were presented as mean ± SD for continuous variables, and as numbers with percentages for categorical variables. The Student’s test was used for continuous variables and Pearson χ² test or Fisher’s exact test for categorical variables. All statistical analyses were performed using STATA software. P < 0.05 was considered to indicate statistical significance.

A total of 21 males (53.8%) and 18 females (46.2%) were included in the study. The mean age was 51.1 years (standard deviation: 10.9). There were 32 non-smokers and seven current or ex-smokers. Of the 39 patients, 27 were asymptomatic (69.2%), and presented with an incidental finding of pulmonary lesions following routine health examinations. In the other 12 patients, symptoms including cough (n = 6), sputum (n = 6), chest pain (n = 4), chest distress (n = 3), hemoptysis (n = 1), and fever (n = 1) were observed. In terms of comorbidities, nine patients had hypertension, eight had a malignancy, two had previous environmental exposures (a clear history of exposure to sulfides (n = 1) or coal (n = 1)), one had severe diabetes mellitus, one received bilateral kidney transplantation, and one had a previous history of pulmonary tuberculosis. For host immune status, 29 patients were immunocompetent. The other 10 patients were considered immunocompromised, including eight patients with a malignancy, one with organ transplantation and diabetes mellitus, and one with tuberculosis receiving antituberculosis drugs. Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients (48.9 vs 57.1 years, P = 0.02). None of the patients had AIDS at the time of diagnosis of PC. 38 patients were diagnosed with PC using surgical modality and only one patient was diagnosed using percutaneous translung biopsy before surgery. Type of surgery included wedge resection (n = 22), segmentectomy (n = 3), and lobectomy (n = 14). The initial suspected diagnosis before surgical resection of the lesion(s) was primary lung cancer in 20 lesions, pulmonary metastasis in five lesions, non-specific granulomatous disease in six lesions, pulmonary tuberculosis in two lesions, infectious disease in two lesions, benign lesions in nine lesions, and hamartoma in two lesions. Immunocompromised patients were more likely to obtain initial diagnosis of pulmonary metastasis than immunocompetent patients (P = 0.001). Patient demographic and clinical information is summarized in Table 1.

The thoracic CT findings are summarized in Table 2. Single nodule pattern was the most frequent lesion pattern, presenting in 33 of the 39 (84.6%) patients, followed by scattered nodule (7.7%), clustered nodule (5.1%), and mass-like (2.5%) (Fig. 1). Pleural effusion was not seen in any patient and mediastinal lymph node enlargement was observed in 10 patients. Most lesions were located in the right upper lobe (15 lesions, 31.9%), followed by right lower lobe (13 lesions, 27.6%) and left lower lobe (13 lesions, 27.6%). Pulmonary lesions (38 out of 47, 80.9%) were located mostly in the peripheral lung field (outer third of the lung). The diameter of the lung lesions was less than 1 cm in nine lesions (19.1%), 1–2 cm in 30 lesions (63.8%), and greater than 2 cm in eight lesions (17%). 20 (42.6%) lesions were spiculated. Air bronchogram was noted in three lesions (6.4%), halo sign in nine (19.1%), and pleural indentation in 10 (21.3%). Cavitation was noted in 11 lesions and was more likely to occur in immunocompromised patients (5 out of 11, 45.5%) than in immunocompetent patients (6 out of 36, 16.7%) (P = 0.04).

The PET/CT results are summarized in Table 3. A total of 14 patients underwent PET/CT scans. SUV_max ranged from 1.8 to 43.5 (average 9.12 ± 10.46, median 6.3). All of the patients showed higher FDG uptake in the pulmonary lesions and four patients revealed higher uptake in lymph node areas. There was no significant difference in SUV_max between immunocompetent and immunocompromised patients (P = 0.49).

Diagnosis of PC was confirmed in all patients by postoperative pathology. H&E staining showed a variety of inflammatory reactions from inflammation to well-formed granulomas, accompanied by various degrees of fibrosis and necrosis (Fig. 2). The presence of the cryptococcal pathogen was identified in all samples by histochemically staining with Gomori methenamine silver (GMS) and periodic acid-Schiff (PAS).

The follow-up period for the patients ranged from 2.5 to 48 months (mean, 11.8 months). Of the 38 patients who were diagnosed by surgery, one patient was lost to follow up and the remaining 37 patients received postoperative antifungal therapy (fluconazole 400 mg/day). The duration of the antifungal therapy ranged from 2 weeks to 8 months (mean, 3.5 months). One patient obtained the diagnosis of PC before surgery. She received oral fluconazole (400 mg/day) for 6 months preoperatively and 3 months postoperatively. All of the 38 patients who received follow-up were completely cured after treatment.