Clinical features Compared to immunosuppressed patients, immunocompetent patients with pulmonary cryptococcosis are more common in males and middle-aged and young adults, and often present with nonspecific pulmonary or systemic clinical symptoms at the onset of illness, which are usually mild. The incidence of clinical symptoms is significantly lower than in immunosuppressed patients, with cough, fever and chest pain being more common and hemoptysis and shortness of breath being less common. Approximately 20-30% of patients have no clinical symptoms, and most of them are detected during physical examination, thus easily misdiagnosed as lung cancer. The imaging manifestations of pulmonary cryptococcosis are varied and non-specific, and may include: (1) isolated mass shadow, mostly in primary pulmonary cryptococcosis; (2) single or multiple nodular shadow; (3) single or multiple patchy shadow, with cavity formation in about 10% of patients, often secondary to pulmonary cryptococcosis; (4) diffuse cornual shadow; (5) acute interstitial pneumonia type, which is rare (5) acute interstitial pneumonia, which is rare. Patients with immunocompetent pulmonary cryptococcosis show mainly single or multiple nodules with varying diameters on chest CT, followed by masses, patchy infiltrates, solid shadows, hairy glass shadows, and some mixed lesions. The lesions are mostly peripheral or subpleural in distribution and may be accompanied by bronchial inflation signs, cavitation signs and halo signs. Mediastinal lymph node enlargement and pleural effusion are less common; while immunosuppressed patients are more likely to have exudative changes (80%). Notably, pediatric patients tend to have enlarged thoracoabdominal lymph nodes, which is a more important differentiator from immunocompetent adults with cryptococcosis: it may be related to the fact that the immune mechanism is not well developed in children and the pathogen is prone to disseminate along the lymph nodes, causing lymph node enlargement. It has been suggested that elderly patients with a gross glass shadow on chest CT, with or without nodules, need to be alerted to the possibility of pulmonary cryptococcosis. In conclusion, the imaging manifestations of pulmonary cryptococcosis lack specificity, and the clinical diagnosis still needs to be clarified in combination with other ancillary tests. Laboratory diagnosis Because the positive rate of cryptococcal culture in sputum and alveolar lavage fluid is not high, previous reports of pulmonary cryptococcosis are mostly surgical confirmed cases. Nowadays, lung biopsy, such as percutaneous pulmonary puncture or minimally invasive tests such as fiberoptic bronchoscopy, is mainly used to clarify the diagnosis. The increase in the diagnosis rate of pulmonary cryptococcosis in recent years is closely related to the widespread implementation of lung biopsy. Therefore, patients with a high clinical suspicion of pulmonary cryptococcosis should undergo percutaneous lung aspiration biopsy as early as possible to avoid delaying the diagnosis and to facilitate the differential diagnosis with other diseases, especially lung cancer and tuberculosis. Treatment There is a lack of prospective clinical trial studies on the treatment of patients with immunocompetent pulmonary cryptococcosis, and the findings are mainly from retrospective surveys and case reports. Current treatment includes pharmacological intervention, surgical resection and clinical observation. In immunosuppressed and immunocompetent patients with mild to moderate pulmonary cryptococcosis, fluconazole 400 mg/d, doubled in the first dose, is preferred for pharmacological treatment. Oral administration for 6-12 months. For those who cannot tolerate fluconazole, itraconazole (200 mg every 12 hours), voriconazole (200 mg every 12 hours) and posaconazole (400 mg every 12 hours) can be given orally; in case of severe pulmonary cryptococcosis, the treatment regimen for central nervous system cryptococcal infections should be adopted by giving amphotericin B combined with flucytosine induction therapy followed by sequential oral fluconazole . Positive serum antigen titers are not a basis for continued treatment. If imaging improvement is not obvious after treatment and symptoms persist, surgical treatment should be considered. The low dose (200 mg/d) and short duration (less than six months) of fluconazole treatment in China should be taken seriously. In recent years, foreign guidelines and clinical studies have recommended high-dose fluconazole treatment for patients with severe disease. For example, if amphotericin B combined with flucytosine is used as induction therapy in the recommended treatment regimen for cryptococcal meningitis in non-HIV-infected and non-transplant recipients, the recommended dose of fluconazole for the consolidation phase of therapy If patients cannot receive amphotericin B therapy due to various circumstances and fluconazole is used directly as induction therapy, the dose of fluconazole should be ≥800 mg/d,1200 mg/d is more effective, or even The dose of fluconazole should be ≥800 mg/d, 1200 mg/d is more effective, even up to 1600-2000 mg/d, for our clinicians’ reference. Surgical treatment can be considered for patients with no obvious effect of antifungal treatment, but the surgery should avoid squeezing the lesion to prevent the spread of the lesion. For patients with obvious respiratory symptoms and infiltrative distribution of lesions, antifungal treatment should be given for at least 6 months after surgery, and failure to treat or discontinuation of treatment may result in serious consequences such as recurrence, spread of lesions (especially to the central nervous system), and even death. Antifungal treatment may be withheld in the absence of underlying disease, limited lesions, low titers of Cryptococcus podococcal polysaccharide antigen, and complete surgical excision. However, since most of the above conclusions are from small retrospective studies and treatment options are still controversial, clinical studies with large prospective clinical controlled trials are needed to provide more convincing evidence. Clinical Guidance Implications The clinical management of patients with immunocompetent pulmonary cryptococcosis differs from that of immunosuppressed patients. The vigilance of pulmonary cryptococcosis should not be relaxed because of normal immune function or negative serum cryptococcal podococcal polysaccharide antigen, which may lead to misdiagnosis or delayed diagnosis and affect the therapeutic effect. Early and aggressive percutaneous lung aspiration biopsy is an important method for timely diagnosis of such patients. At the same time, adequate doses and sufficient courses of antifungal therapy are extremely important to improve the cure rate and reduce the recurrence rate.