• antifungal therapy
• dose optimization
• fluconazole
• lean bodyweight
• obese
• pulmonary cryptococcosis

• Health Commission of Hubei Province

• adenosine deaminase
• cryptococcal antigen
• cryptococcal pleural effusion

• Cryptococcus
• Infections
• Meningitis
• Pleural infection

• Female
• Humans
• Cryptococcus neoformans
• Antifungal Agents/therapeutic use
• Temozolomide/adverse effects
• Cryptococcosis/diagnosis
• Cryptococcosis/drug therapy
• Cryptococcosis/complications
• Fluconazole/adverse effects
• Pleural Effusion/chemically induced
• Pleural Effusion/diagnostic imaging
• Pleural Effusion/complications
• Steroids

• immunocompromised
• pleural biopsy
• pleural cryptococcosis
• pleural effusion
• thymoma

• Humans
• Pleura
• Cryptococcosis/microbiology
• Pleural Effusion
• Biopsy/adverse effects
• Immunocompromised Host

• Antifungal resistance
• Antifungal tolerance
• Cryptococcal meningitis
• Cryptococcus neoformans
• Fungal infections

• Humans
• Cryptococcus neoformans
• Meningitis, Cryptococcal/drug therapy
• Meningitis, Cryptococcal/epidemiology
• Meningitis, Cryptococcal/complications
• Antifungal Agents/pharmacology
• Antifungal Agents/therapeutic use
• HIV Infections/drug therapy
• Mycoses/complications
• Mycoses/drug therapy

• 2022YFC2303000 National Key Research and Development Program of China
• 2021YFC2300400 National Key Research and Development Program of China
• 30900880 Henan Agricultural University
• 30500946 Henan Agricultural University
• CAS Interdisciplinary Innovation Team

Pleural involvement of cryptococcal infection is uncommon and is more commonly observed in immunocompromised hosts than in immunocompetent ones. Pleural involvement in cryptococcal infections can manifest with or without pleural effusion. The presence of Cryptococcus spp. in the effusion or pleura is required for the diagnosis of cryptococcal pleural infection, which is commonly determined by pleural biopsy, fluid culture, and/or detection of cryptococcal antigen in the pleura or pleural fluid.

• Cryptococcosis
• Pleural effusion
• Pleural diseases
• Fungal lung diseases
• Pleural Cavity
• Cryptococcus neoformans

• mesothelial
• mesothelioma in situ
• non-specific pleuritis
• pleura
• pleural effusion
• pleural pathology

• Cryptococcosis/complications
• Cryptococcosis/diagnosis
• Exudates and Transudates
• HIV Infections/complications
• Humans
• Pleural Effusion/etiology

To our knowledge, this is the first case report of a transudative pleural effusion with positive Cryptococcal antigen and culture. We describe a 32-year-old male with end-stage liver disease (ESLD) who presented to an outside hospital with dyspnea and a large pleural effusion. An initial pleural fluid analysis was positive for Cryptococcal Ag. However, the infection was eventually found to be widespread as he had positive Cryptococcal Ag and cultures in his pleural fluid, serum, and cerebrospinal fluid (CSF). His antimicrobial regiment was escalated from fluconazole to amphotericin B and flucytosine. His medical condition deteriorated, and the patient passed away. Due to its rarity and range of clinical severity, diagnosis of disseminated Cryptococcosis can be delayed. We present this case to bring awareness of this diagnosis as a differential in immunocompromised patients regardless of a transudative pleural effusion.

• Cirrhosis
• Cryptococcus
• Disseminated
• Pleural effusion
• Transudative

• ADA, adenosine deaminase
• ALP, alkaline phosphatase
• ALT, alanine transaminase
• AST, aspartate aminotransferase
• CRP, C-reactive protein
• CT, computerized tomography
• Diabetes mellitus
• ESR, erythrocyte sedimentation rate
• FiO2, fraction of inspired oxygen
• Fungal infection
• GGT, gamma glutamyl transferase
• HIV, human immunodeficiency virus
• Hb, hemoglobin
• Ht, hematocrit
• LDH, serum lactate dehydrogenase
• PTLS, platelets
• Pleural effusion
• SG, specific gravity
• TSH, thyroid-stimulating hormone
• Trichoderma longibrachiatum
• WBC, white blood cells

This study aimed to compare the clinical features of pulmonary cryptococcosis (PC) in patients with and without central nervous system (CNS) involvement.

We retrospectively reviewed demographics, presenting symptoms, radiographic features, and laboratory findings of patients diagnosed with PC in 28 hospitals from 2010 to 2019. Risk factors for CNS involvement were analyzed using logistic regression models.

A total of 440 patients were included, and 36 (8.2%) had CNS involvement. Significant differences in fever, headache, and chills occurred between the two groups (overall and with/without CNS involvement) for fever (17.8% [78/440]; 52.8% vs. 14.6% of patients, respectively), headache (4.5% [20/440]; 55.6% vs. 0% of patients, respectively), and chills (4.3% [19/440]; 13.9% vs. 3.5% of patients, respectively). The common imaging manifestation was nodules (66.4%). Multivariate analysis showed that cavitation (adjusted odds ratio [AOR] = 3.552), fever (AOR = 4.182), and headache were risk factors for CNS involvement. Routine blood tests showed no differences between the groups, whereas in cerebrospinal fluid the white blood cell count increased significantly and glucose decreased significantly.

In patients with PC, the risk of CNS involvement increases in patients with headache, fever, and cavitation; these unique clinical features may be helpful in the diagnosis.

• Cryptococcus neoformans
• cryptococcosis
• cytokines
• granuloma
• kidney transplantation
• regulatory T cells

Pulmonary Cryptococcosis is a common fungal infection mainly caused by Cryptococcus neoformans/C.gattii species in immunocompromised patients. Cases of pulmonary cryptococcosis in patients with normal immune function are increasingly common in China. Clinical and radiographic features of pulmonary cryptococcosis are various and without obvious characteristics, so it is often misdiagnosed as pulmonary metastatic tumor or tuberculosis. When coexisting with malignant lung tumors, it was more difficult to differentiate from metastatic lung cancer, although the coexistence of pulmonary cryptococcosis and central type lung cancer is rare. Reviewing the imaging manifestations and diagnosis of the case and the relevant literature will contribute to recognition of the disease and a decrease in misdiagnoses.

A 72-year-old immunocompetent Han Chinese man had repeated dry cough for more than half a year. CT examination of chest showed an irregular mass at the left hilum of the lung, and two small nodules in the right lung, which were considered as the left central lung cancer with right lung metastasis. However, the patient was diagnosed with pulmonary cryptococcosis coexisting with central type lung cancer based on the results of laboratory examination, percutaneous lung biopsy, fiberoptic bronchoscopy, and surgical pathology. The patient underwent surgical resection of the left central type lung cancer and was placed on fluconazole treatment after a positive diagnosis was made. Five years after the lung cancer surgery, the patient had a recurrence, but the pulmonary cryptococcus nodule disappeared.

Our case shows that CT findings of central type lung cancer with multiple pulmonary nodules are not necessarily metastases, but may be coexisting pulmonary cryptococcosis. CT images of cryptococcosis of the lung were diverse and have no obvious characteristics, so it was very difficult to distinguish from metastatic tumors. CT-guided percutaneous lung biopsy was a simple and efficient method for identification.

• CT-guided percutaneous lung biopsy
• Central type lung cancer
• Computed tomography
• Cryptococcosis
• Metastatic tumor
• PAS periodic acid-Schiff

• Criptococosis pulmonar
• Cryptococcus neoformans
• HIV
• Histopathology
• Histopatología
• Pulmonary cryptococcosis
• VIH

Pulmonary Cryptococcosis (PC) is diagnosed with increasing incidence in recent years, but it does not commonly involve the pleural space. Here, we report a HIV-negative case with advanced stage IIIB non-small cell lung cancer (NSCLC) treated with radiation therapy presented with dyspnea, a new PET-positive lung mass and bilateral pleural effusion suspecting progressive cancer. However, the patient has been diagnosed as pulmonary cryptococcal infection and successfully treated with oral fluconazole therapy.

A 77-year-old male with advanced stage non-small cell lung cancer treated with combined chemo-radiation therapy who presented with progressive dyspnea, a new PET-positive left lower lobe lung mass and bilateral pleural effusions. Initial diagnostic thoracentesis and bronchoscopy yielded no cancer, but instead found yeast forms consistent with cryptococcal organisms in the transbronchial biopsies of the left lower lobe lung mass. Subsequent to this, the previously collected pleural fluid culture showed growth of Cryptococcus neoformans. The same sample of pleural effusion was tested and was found to be positive for crytococcal antigen (CrAg) by a lateral flow assay (LFA). The patient has been treated with oral fluconazole therapy resulting in gradual resolution of the nodular infiltrates.

PC should be considered in immunosuppressed cancer patients. Additionally, concomitant pleural involvement in pulmonary cryptococcal infections may occur. The incidence of false positive ¹⁸FDG-PET scans in granulomatous infections and the use of CrAg testing in pleural fluid to aid in diagnosis are reviewed.

• Crytococcal antigen
• Lateral flow assay
• Pleural effusion
• Pulmonary cryptococcosis

• cryptococcosis
• cryptococcus neoformans
• hepatic cirrhosis
• multilocus sequence typing (mlst)
• pleuritis

• Cryptococcosis/complications
• Cryptococcosis/diagnosis
• Cryptococcosis/drug therapy
• Diagnosis, Differential
• Hepatitis B/complications
• Hepatitis B/diagnosis
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Male
• Middle Aged
• Pleural Effusion/complications
• Pleural Effusion/diagnosis
• Pleural Effusion/drug therapy
• Pleurisy/complications
• Pleurisy/diagnosis
• Pleurisy/drug therapy

Diagnosis of invasive cryptococcal infection in apparently nonimmunocompromised patients is difficult and often delayed. Human immunodeficiency virus- (HIV-) negative patients with decompensated hepatic cirrhosis might be at high risk of cryptococcal infection. We report here an 82-year-old Japanese female with end-stage hepatic failure and undergoing renal dialysis, hospitalized with septic shock-like symptoms. The patient had had hepatitis B virus (HBV) infection in the past. She survived only 4 days following admission. During hospitalization, she was found to have pleural effusion and ascites. Cryptococcus neoformans was obtained from blood culture but not from pleural effusion culture. Consequently, the patient was diagnosed as having invasive cryptococcosis in association with HBV-related hepatic cirrhosis. Unfortunately, the patient died prior to receiving antifungal agents. Twelve Japanese cases of hepatic cirrhosis-related invasive cryptococcal infection, consisting of previously described and this case, were summarized for discussion of the clinical features and outcomes.

Pulmonary cryptococcosis is a common fungal infection frequently seen in immunocompromised patients. Owing to its nonspecific clinical and radiographic features, the differential diagnosis with secondary tuberculosis, malignant tumor, and bacterial pneumonia is sometimes difficult. Many case reports have focused on misdiagnosis of pulmonary cryptococcosis as a malignant tumor. But to the best of our knowledge, the coexistence of pulmonary cryptococcosis and malignant tumor is rarely presented.

A 52-year-old immunocompetent Han Chinese woman was presented to our emergency department complaining of headache and vomiting accompanied by postural changes. She was diagnosed with pulmonary cryptococcosis according to results of laboratory tests, computed tomography, and percutaneous lung biopsy. Owing to the poor therapeutic effects of 6-month fluconazole treatment, she underwent a second percutaneous lung biopsy and was diagnosed with pulmonary cryptococcosis coexisting with adenocarcinoma. Delayed treatment of malignant tumor resulted in lymph node metastasis, higher pathologic stage, and probably poorer prognosis.

Our patient’s case serves as a reminder not to misdiagnose pulmonary cryptococcosis coexisting with adenocarcinoma.

• Abbreviations
• Adenocarcinoma
• CEA Carcinoembryonic antigen
• CRP C-reactive protein
• CT Computed tomography
• Fungal infection
• PAS Periodic acid-Schiff
• PCT Procalcitonin
• Pneumonia
• Pulmonary cryptococcosis

• cryptococcosis
• cryptococcus
• empyema
• pleural infection
• tyrosine kinase inhibitor

• adenosine deaminase
• co-infection
• cryptococcal antigen test
• cryptococcal pleuritis
• pulmonary tuberculosis

• Adenosine Deaminase/analysis
• Aged, 80 and over
• Anti-Inflammatory Agents/therapeutic use
• Coinfection/drug therapy
• Coinfection/microbiology
• Coinfection/physiopathology
• Cryptococcosis/drug therapy
• Cryptococcus neoformans/isolation & purification
• Humans
• Lymphocytes/chemistry
• Male
• Mycobacterium tuberculosis/isolation & purification
• Pleura/microbiology
• Pleura/physiopathology
• Pleural Effusion/microbiology
• Pleurisy/microbiology
• Prednisone/therapeutic use
• Treatment Outcome
• Tuberculosis, Pleural/drug therapy
• Tuberculosis, Pleural/microbiology
• Tuberculosis, Pleural/physiopathology
• Tuberculosis, Pulmonary/drug therapy
• Tuberculosis, Pulmonary/microbiology
• Tuberculosis, Pulmonary/physiopathology