Diagnosis Of Pulmonary Cryptococcosis Research Articles

Establishment of a predictive model of CT value in the diagnosis and differential diagnosis of pulmonary cryptococcosis

ObjectiveTo investigate the application value of computed tomography (CT) value (HU) in the diagnosis and differential diagnosis of pulmonary cryptococcosis (PC) and to construct a prediction model. MethodsRetrospective analysis of the clinical data of 73 patients who presented with nodular/mass-type occupations on lung CT and confirmed by histopathology in our hospital from January 2019 to May 2022 were divided into PC group (23 patients) and non-PC group (50 patients) according to the pathological findings, and the CT values of each patient's lung lesions were measured. The differences in age, gender, symptoms, lesion involvement in one/both lungs, lung lobe distribution, number of lesions, maximum lesion diameter (cm), lesion margin condition, and CT value results were compared between the two groups. Independent risk factors for PC were analyzed for indicators with statistically significant differences, clinical prediction models were constructed and column line plots were drawn, C (correction) indices were calculated, subject characteristics (ROC) curves were drawn, calibration curves and clinical decision curve analysis (DCA) were performed to further evaluate the predictive efficacy of the models. ResultsComparative analysis of patient data between the two groups showed statistically significant differences in central, peripheral and global CT values (P < 0.05), and multiple regression analysis indicated that central CT value, peripheral CT value and global CT value could be used as independent risk factors for the diagnosis and differential diagnosis of PC. The area under the ROC curve of the model predicting PC was 0.814 (95 % CI: 0.7011–0.9267), and the corrected C-index (Bootstrap = 1000) was 0.781; the actual curve overlapped well with the calibration curve; the DCA results indicated that the column line graph model has high clinical application value. ConclusionsCT value measurements of lesions can be used as an independent risk factor for PC, and clinical prediction models based on the above factors are predictive for the diagnosis and differential diagnosis of PC.

Value of rapid on-site evaluation combined with interventional pulmonology techniques in the diagnosis of pulmonary cryptococcosis.

The aim of this study is to evaluate the diagnostic value of rapid on-site evaluation (ROSE) combined with computed tomography-guided percutaneous needle biopsy (CT-PNB) or radial endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) for pulmonary cryptococcosis (PC). Clinical data of 33 patients diagnosed with PC at the Third Affiliated Hospital of Soochow University between February 2018 and June 2023 were retrospectively analysed. Patients were divided into the CT-PNB and EBUS-TBLB groups based on the intervention method, and the diagnostic positivity rate and incidence of complications were compared between the two groups. Compared with the final diagnosis, the positive diagnostic rates of ROSE, histopathology and serum CrAg of all patients were 81.8% (27/33), 72.7% (24/33) and 63.6% (21/33), respectively. The average turnaround times of the three methods were 0.1 (0.1-0.2) h, 96.0 (48.0-120.0) h and 7.8 (4.5-13.6) h, respectively (P <0.001). The coincidence rate between histopathology and ROSE was 84.8% with a kappa value of 0.574. The positive diagnostic rate for PC was significantly higher in the CT-PNB group than in the EBUS-TBLB group (92.9% vs. 57.9%), and the difference was statistically significant (P <0.05). Combined with the ROSE results, the positive diagnostic rate in the EBUS-TBLB group increased to 84.2% (16/19). ROSE has commendable accuracy and timeliness, and CT-PNB offers further advantages in this regard. ROSE enhances the diagnostic efficiency of EBUS-TBLB for PC and is safe and effective.

A CT-based radiomics integrated model for discriminating pulmonary cryptococcosis granuloma from lung adenocarcinoma-a diagnostic test.

Chest computed tomography (CT) is a critical tool in the diagnosis of pulmonary cryptococcosis as approximately 30% of normal immunity individuals may not exhibit any significant symptoms or laboratory findings. Pulmonary cryptococcosis granuloma and lung adenocarcinoma can appear similar on noncontrast chest CT. This study evaluates the use of an integrated model that was developed based on radiomic features combined with demographic and radiological features to differentiate pulmonary cryptococcosis nodules from lung adenocarcinomas. Preoperative chest CT images for 215 patients with solid pulmonary nodules with histopathologically confirmed lung adenocarcinoma and cryptococcosis infection were collected from two clinical centers (108 cases in the training set and 107 cases in the test set divided by the different hospitals). Radiomics models were constructed based on nodular lesion volume (LV), 5-mm extended lesion volume (ELV), and perilesion volume (PLV). A demoradiological model was constructed using logistic regression based on demographic information (age, sex) and 12 radiological features (location, number, shape and specific imaging signs). Both models were used to build an integrated model, the performance of which was assessed using the test set. A junior and a senior radiologist evaluated the nodules. Receiver operating characteristic (ROC) curve analysis was conducted, and areas under the curve (AUCs), sensitivity (SEN), and specificity (SPE) of the models were calculated and compared. Among the radiomics models, AUCs of the LV, ELV, and PLV were 0.558, 0.757, and 0.470, respectively. Age, lesion number, and lobular sign were identified as independent discriminative features providing an AUC of 0.77 in the demoradiological model (SEN 0.815, SPE 0.642). The integrated model achieved the highest AUC of 0.801 (SEN 0.759, SPE 0.755), which was significantly higher than that obtained by a junior radiologist (AUC =0.689, P=0.024) but showed no significant difference from that of the senior radiologist (AUC =0.784, P=0.388). An integrated model with radiomics and demoradiological features improves discrimination of cryptococcosis granulomas from solid adenocarcinomas on noncontrast CT. This model may be an effective strategy for machine complementation to discrimination by radiologists, and whole-lung automated recognition methods might dominate in the future.

Comparison of different therapeutic approaches for pulmonary cryptococcosis in kidney transplant recipients: a 15-year retrospective analysis.

Organ transplant recipients are at increased risk of developing pulmonary cryptococcosis (PC) due to weakened cell-mediated immunity caused by immunosuppressors. However, the nonspecific symptoms associated with PC can often lead to misdiagnosis and inappropriate treatment. We conducted a retrospective analysis of data from 23 kidney transplant recipients with PC between April 2006 to January 2021. The median time from transplantation to the diagnosis of pathology-proven PC 4.09 years. Seventeen patients presented respiratory symptoms, including sputum-producing cough and dyspnea. Additionally, three patients also developed central nervous system (CNS) infections. Chest CT scans frequently revealed nodule-shaped lesions, which can mimic lung carcinoma. Serological tests did not demonstrate any specific changes. Nine patients received surgical resection as treatment. Fourteen patients were treated with antifungal medication only. No recurrence was observed in all 23 patients. Our study suggests that fever and sputum-producing cough are common symptoms of PC, and cryptococcal meningitis should not be excluded if corresponding symptoms occur. Fluconazole is a common and effective antifungal agent. Surgical resection should be considered for patients who do not respond well to antifungal therapy. Clinicians should be aware of these findings when evaluating transplant recipients with respiratory symptoms.

Video-assisted thoracoscopic surgery for primary pulmonary cryptococcosis

The surgical outcome for primary pulmonary cryptococcosis remains unclear. In this study, we investigated the clinical characteristics, treatment, and outcomes of video-assisted thoracoscopic surgery (VATS) for primary pulmonary cryptococcosis. We retrospectively reviewed the medical records of 49 patients with confirmed pulmonary cryptococcosis who underwent VATS for pulmonary nodules at the National Taiwan University Hospital between May 2013 and March 2019. Serum cryptococcal antigen (CryAg)-positive and CryAg-negative patients were compared. The diagnosis of pulmonary cryptococcosis was confirmed using histopathology or tissue swab culture. The mean age of the patients was 56.0±12.2 years, and 27 patients (55.1%) were male. Most patients were asymptomatic (67.3%) and admitted following the detection of pulmonary lesions on a computed tomography scan of the chest. A greater proportion of patients in the CryAg-positive group (62.5%) underwent lobectomy compared with those in the CryAg-negative group (7.3%, P<0.001). Three patients (6.1%) had neurological symptoms (headache or dizziness) and all were serum CryAg-positive. One patient with Cryptococcus gattii developed fluctuating serum CryAg titers after a 12-month antifungal treatment. No relapse occurred in the remaining 48 patients, irrespective of postoperative antifungal treatment. In patients with primary pulmonary cryptococcosis, serum CryAg detection rate is low, and VATS was an effective and safe diagnostic and therapeutic tool.

Grocott Methenamine Silver Staining Is the Optimal Approach to Histological Diagnosis of Pulmonary Cryptococcosis.

BackgroundHistological staining methods for Cryptococcus identification vary in accuracy. This study aimed to investigate the clinical value of Grocott methenamine silver (GMS), periodic acid-Schiff (PAS), and Alcian blue (AB) staining in the diagnosis of pulmonary cryptococcosis (PC).MethodsFrom April 2004 to June 2021, the clinical and pathological data of 152 patients with PC were collected from the Department of Pathology, Sun Yat-sen University Cancer Center. The sensitivity and identifiability of GMS, PAS, and AB staining for histological diagnosis were systematically evaluated using statistical methods combined with the microscopic characteristics of PC cases.ResultsStatistical analysis showed that the detection rates of GMS, PAS, and AB staining were 100.0% (152/152), 94.7% (144/152), and 81.6% (124/152), respectively. McNemar’s test showed that the sensitivity of GMS was significantly higher than those of PAS (P = 0.008) and AB stains (P < 0.001). Both PAS and AB stains had obvious non-specific staining, which interfered with the detection of Cryptococcus, and increased diagnostic difficulties. In contrast, in GMS staining, Cryptococcus spores were prominent with a clean background and were clearly observed at low or medium power magnification, with the identifiability significantly better than those of PAS or AB staining.ConclusionGMS staining had sensitivity up to 100%, and identifiability that was better than those of PAS and AB staining. GMS is the best method for histological diagnosis of PC.

Cryptococcal antigen testing of lung tissue homogenate improves pulmonary cryptococcosis diagnosis: Two case reports

BACKGROUNDPulmonary cryptococcosis (PC) is an opportunistic infectious disease of the respiratory system. Lung tissue biopsies, culture of respiratory samples (e.g., sputum, lung tissue, pleural fluid, and bronchoalveolar lavage fluid), and cryptococcal antigen (CrAg) testing are helpful for a definitive diagnosis. However, these tests are sometimes falsely negative. PC is often misdiagnosed or underdiagnosed owing to the absence of obvert symptoms, poor imaging specificity, and false-negative laboratory tests.CASE SUMMARYWe report two female patients who underwent computed tomography-guided percutaneous needle pulmonary biopsy of a lung nodule for a confirmed diagnosis. In both patients, the CrAg test on the lung biopsy tissue homogenate was positive, while the serum CrAg test was negative. Combined with the lung tissue pathology, we made the diagnosis of PC. Antifungal therapy was effective in both patients.CONCLUSIONGiven the findings of our cases and the literature review, lung tissue homogenate CrAg testing can be helpful in improving the diagnosis of PC.

Performance of rapid on-site evaluation of touch imprints of lung tissue biopsies for the diagnosis of pulmonary cryptococcosis in patients without HIV infection.

The diagnosis of pulmonary cryptococcosis depends on serum testing, histopathology and mycological culture; there are few studies on touch imprints of lung tissue biopsies for the diagnosis of pulmonary cryptococcosis in patients without HIV infection. The purpose of the current study was to investigate the accuracy and timeliness of on-site touch imprint cytology in the diagnosis of pulmonary cryptococcosis during CT-guided percutaneous lung biopsy. We retrospectively analysed the diagnosis and treatment of 56 patients with final proof of pulmonary cryptococcosis through histopathology and culture or surgical resection from September 2015 to February 2021. Diagnostic methods and treatment and the turnaround time for diagnosis were analysed. The sensitivity of rapid on-site evaluation was 89.3%, and the sensitivity of serology, histopathology and mycological culture was 53.6%, 91.1% and 61.5%, respectively, compared with the final diagnosis. The average turnaround time to diagnose pulmonary cryptococcosis by on-site touch imprint cytology was 8.3±0.9min, which was significantly faster than serum testing, histopathology and mycological culture. On-site touch imprint cytology showed good sensitivity and timeliness in the diagnosis of pulmonary cryptococcosis. In addition, it contributed to the triage of biopsies based on the preliminary diagnosis. On-site touch imprint cytology should be applied and promoted in the diagnosis of pulmonary cryptococcosis during biopsy.

Crazy\u2010paving patterns as rare radiological manifestations of pulmonary cryptococcosis: a case report

BackgroundCrazy-paving patterns are rarely reported as radiological manifestations of pulmonary cryptococcosis.Case presentationHerein, we presented a very rare case of a crazy-paving pattern as a radiological manifestation of pulmonary cryptococcosis in a patient with primary ciliary dyskinesia. The diagnosis of pulmonary cryptococcosis and primary ciliary dyskinesia was ultimately confirmed by bronchoscopic biopsy, fungus culture, whole exome sequencing of blood, etc. The patient received flucytosine (PO, 5 g per day) and amphotericin B (IV, 70 mg per day) during hospitalization and sequential therapy with voriconazole (PO, 200 mg twice a day) after discharge. He recovered during follow-up.ConclusionsWe concluded that pulmonary cryptococcosis should be considered a possible cause of crazy-paving patterns in chest CT scans.

Imaging Findings of Pulmonary Cryptococcosis

Pulmonary cryptococcosis(PC)is a fungal infection that can be easily misdiagnosed due to its non-specific clinical features and imaging findings.This article reviews the imaging findings of PC,their relationships with pathology and immune status,and differential diagnosis of PC with other disease,so as to improve the clinical management of PC.

The performance of serum cryptococcal capsular polysaccharide antigen test, histopathology and culture of the lung tissue for diagnosis of pulmonary cryptococcosis in patients without HIV infection.

BackgroundClinicians may fail to make an early diagnosis of pulmonary cryptococcosis (PC) without HIV infection. Serum cryptococcal capsular polysaccharide antigen (CrAg) test, histopathology and culture of lung tissue play different roles in diagnosis of PC.ObjectiveTo investigate the performance of serum CrAg test, histopathology and culture of the lung tissue in diagnosis of PC without HIV infection.Patients/methodsFrom January 2011 to September 2017, patients with proven PC were recruited from a teaching hospital in southern China. Those patients with HIV infection, PC confirmed by surgery or PC with probable or possible diagnosis were excluded from the study. Latex agglutination test and CrAg lateral flow assay were used for detection of serum CrAg. Lung biopsy and needle aspiration were performed under computed tomography guidance.ResultsEighty-nine patients with proven PC including 41 male (46.1%) and 48 female (53.9%) were enrolled. Fifty-one (57.3%) patients had underlying disease. Positive CrAg test was found in 83 (93.3%) cases. Among six cases with negative CrAg test, PC was confirmed by histology in two cases and positive culture in four cases. The histopathological results of 77 (86.5%) cases revealed cryptococcal granuloma and 12 cases showed chronic inflammation, which was confirmed by positive culture. Among 65 cases, the diseased tissue of 46 (70.8%) cases presented Cryptococcus neoformans in the culture and one case was diagnosed with lung cancer coexisting with PC.ConclusionOur findings showed that serum CrAg test is rapid and sensitive in diagnosing PC, histology is important for confirming PC and culture plays a complementary role. Biopsied lung tissue should be submitted for cultures whenever feasible.

Cryptococcal Meningitis in a HIV-Negative Patient.

Sarcoidosis is a risk factor for the development of cryptococcal infection due to dysfunction at T-cell level. Its rarity may, however, delay diagnosis and treatment. We describe the case of a 60-year-old man, diagnosed with sarcoidosis since 1999. He had never received systemic immunomodulatory therapy, such as corticosteroid therapy. In 2012, he was diagnosed with pulmonary cryptococcosis and treated with fluconazole. In April 2013, he presented with symptoms compatible with central nervous system (CNS) infection, namely, Cryptococcus neoformans meningitis. He was treated with amphotericin B, followed by fluconazole. The clinical outcome was favourable.LEARNING POINTSAlthough rare, in patients with sarcoidosis and central nervous system (CNS) symptomatology, it is important to verify the existence of cryptococcal meningitis.Antifungal treatment should be started as early as possible.Before the diagnosis of pulmonary cryptococcosis, dissemination to the CNS should be outruled due to the need for more aggressive treatment.

Retrospective analysis of 117 cases of pulmonary cryptococcosis

Objective: To investigate the clinical features of pulmonary cryptococcosis(PC). Methods: A total of 117 cases of PC, confirmed by pathological examinations at Fuzhou Pulmonary Hospital of Fujian from January 2009 to December 2013, were studied. Results: The patients consisted of 75 males and 42 females, with a mean age of (44.1±13.7) years (range, 16 to 76 years). Thirty-eight cases were immunocompromised hosts (ICH) and 79 cases were non-immunocompromised hosts (NICH). The clinical symptoms of most patients were mild and the main clinical manifestations were cough and sputum production. The chest CT manifestations were as follows: nodular or mass-like shadows in 66, patchy infiltrates or consolidation in 34, and mixed lesions in 17 cases. There were a variety of CT signs accompanied, with halo sign (78 cases) and proximal air bronchogram (63 cases) being the most common. These two signs were more common in NICH than ICH (77.2%, 44.7%, P=0.001; 60.8%, 39.5%, P=0.047). They were also more likely to be seen in the patchy infiltrates or consolidation and mixed patterns than in nodular or mass-like type of PC(82.4%, 82.4% and 54.5%, P=0.007; 76.5%, 82.4% and 33.3%, P=0.000), while lobulation sign, spicule sign and pleural indentation were more likely to be seen in the latter(0%, 5.9% and 30.3%, P=0.000; 0%, 5.9% and 27.3%, P=0.000; 0%, 5.9% and 19.7%, P=0.005). The lesions of PC were mainly found in the right lung and lower lobes. The lesions in NICH were more commonly seen in multiple lobes than ICH. Enhanced CT scanning was performed in 38 patients, and 24 cases showed uniform enhancement and 27 moderate enhancement. The diagnosis was confirmed in all cases by pathological findings. A hundred and one cases were treated and carefully followed in our hospital except 16 cases who were lost for follow-up. Seventy-one were cured and 30 were improved. Conclusions: The clinical symptoms of PC were diverse and nonspecific. Halo sign and proximal air bronchogram are helpful for the diagnosis of PC. The outcome of most patients was satisfactory after appropriate treatment.

A case of necrotizing glomerulonephritis presenting with nephrotic syndrome associated with pulmonary cryptococcosis

We describe a 68-year-old man with necrotizing glomerulonephritis who presented with nephrotic syndrome accompanied by pulmonary cryptococcosis. He developed rheumatoid arthritis in July 1999 and was treated with low-dose prednisolone. He was admitted to our hospital on November 22 following the appearance of bilateral leg edema in October 2000. Laboratory tests at presentation revealed nephrotic syndrome with renal impairment. Renal biopsy specimens revealed necrotizing glomerulonephritis with crescent, but immunofluorescence study showed lack of staining for immunoglobulins or complement components. Chest X-ray and CT showed abnormal shadows in the right upper lung field, and Cryptococcus neoformans was isolated in a transbronchial lung biopsy. After the diagnosis of pulmonary cryptococcosis was made, the patient was treated with 200 mg/day fluconazole. The pulmonary abnormal shadows immediately improved and urinary protein excretion dramatically decreased. A second renal biopsy, performed about 2 months after the first biopsy, showed disappearance of crescent. Electron microscopic examination of the second renal biopsy showed partial effacement of foot processes without electron-dense deposits. Our findings suggest that necrotizing glomerulonephritis with nephrotic syndrome in this patient represented pauci-immune T-cell-mediated injury related to pulmonary cryptococcosis.

The clinical epidemiology of pulmonary cryptococcosis in non-AIDS patients at a tertiary care medical center.

Cryptococcus neoformans is a ubiquitous saprophytic fungus with worldwide distribution. It has been found in nature, primarily in association with bird droppings, but nonavian sources have been described as well (10). Although the lungs are thought to be the portal of entry for cryptococcus, pulmonary infection is uncommon. The organism is trophic to the central nervous system and the vast majority of recognized infections involve meningitis. Before the acquired immunodeficiency syndrome (AIDS) epidemic (1980), cryptococcosis was a rare infection, and pulmonary disease was described in 10%–45% of patients with cryptococcal meningitis (2). However, the true incidence of pulmonary cryptococcosis (PC) was not known, but was much lower than meningitis. Most PC cases were identified histologically and often at autopsy, with only about 20% diagnosed by culture (2, 3, 13). In recent years, many of the reports of cryptococcal infection have been in the human immunodeficiency virus (HIV)-positive population, and little is known of the disease in non-AIDS patients, particularly pulmonary involvement. At our institution, a tertiary care medical center with a large transplant program, sporadic cases of PC have occurred in solidorgan transplant recipients as well as in patients with a variety of different medical conditions. The purpose of our study was to investigate the epidemiology of PC in non-AIDS patients, and to determine predictors of outcome among these patients.