OBJECTIVE: To improve the understanding of the clinical features of pulmonary cryptococcosis in non-human immunodeficiency virus (non-HIV) infection patients and reduce delay in diagnosis, or misdiagnosis. METHODS: The clinical features, imaging characteristics, laboratory examinations, treatment and prognosis of 34 cases of pulmonary cryptococcosis were retrospectively analyzed. The data were collected from Peking University First Hospital from June 1997 to June 2016. RESULTS: There were 34 cases diagnosed with pulmonary cryptococcosis, including 22 males and 12 females, aged from 20 to 75 years [average: (50.1±15.0) years]. There were 16 cases with host factors and (or) underlying diseases named immunocompromised group. In the study, 67.6% patients had clinical symptoms while 32.4% patients had no symptoms. The most common symptoms included cough, fever, chest pain, shortness of breath, and hemoptysis in sequence. Common chest imaging findings were patchy infiltrates, consolidation, single or multiple nodular or masses shadows. Among the 20 cases with cryptococcal capsular polysaccharide antigen detection, 19 were positive. Eleven cases underwent routine cerebrospinal fluid examination, and 3 cases complicated with central nervous system cryptococcal infection. At first visit, 24 cases were misdiagnosed, among which, 11 cases were misdiagnosed as lung cancer. The diagnosis of 15 cases was proved by percutaneous lung biopsy and 11 were confirmed by surgery, while 8 were diagnosed clinically. Then 11 cases were treated by surgical resection, and in median 4 years' followp, there was 1 case of recurrence. And 23 cases were treated with antifungal therapy, and in median 8 years' follow-up, 3 cases lost to the follow-up and 1 case of recurrence. Compared with normal immune group, immunocompromised patients had higher ages (P=0.017), more crackles (P=0.006) and more percentage of increase of peripheral white blood cells or neutrophils (P=0.003), but no significant difference in symptoms, imaging characteristics or hospitalization time. CONCLUSION There were no specific clinical symptoms and signs for pulmonary cryptococcosis in non-HIV patients. Diagnosis of pulmonary cryptococcosis depends on pathology. Percutaneous lung biopsy was mostly recommended for clinical highly suspected patients. Cryptoeoccal capsular polysaccharide antigen detection had a high sensitivity for the clinical diagnosis. Antifungal drug therapy was the major treatment, and the prognosis of the most patients was good.
Adult ; Aged ; Cryptococcosis/pathology* ; Delayed Diagnosis ; Diagnostic Errors ; Female ; Humans ; Lung Diseases ; Lung Diseases, Fungal/pathology* ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

BackgroundSerum cryptococcal antigen (CrAg) test is the most used noninvasive method to detect cryptococcal infection. However, false-negative CrAg test is not uncommon in clinical practice. Then, the aim of this study was to investigate the factors associated with false-negative CrAg test among non-human immunodeficiency virus (HIV) adult patients with pulmonary cryptococcosis and its clinical features.

MethodsOne hundred and fourteen non-HIV adult patients with pulmonary cryptococcosis, proven by biopsy, were retrospectively reviewed. Finally, 85 patients were enrolled; 56 were CrAg positive (CrAg+ group) and 29 were negative (CrAg- group). It was a cross-sectional study. Then, baseline characteristics, underlying diseases, clinical symptoms, laboratory findings, and chest radiological findings were reviewed and analyzed. Chi-square test was used to analyze categorical variable. Odds ratio (OR) was used to measure correlation. Student's t- test was obtained to analyze continuous variable.

ResultsNo difference in baseline characteristics, underlying diseases, clinical symptoms, and laboratory findings were found between two groups (P > 0.05 in all). Nevertheless, diffuse extent lesion was 82.1% in CrAg+ group and 10.3% in CrAg- group (χ = 40.34, P < 0.001; OR = 39.87).

ConclusionsAmong patients with limited pulmonary involvement, a negative serum CrAg does not preclude the diagnosis of pulmonary cryptococcosis. However, among patients with extensive pulmonary involvement, serum CrAg is a useful diagnostic tool for pulmonary cryptococcosis. Furthermore, we also noticed that the untypical and mild presentations with extensive pulmonary lesion might be the features of pulmonary cryptococcosis, which needs further investigation.

Adolescent ; Adult ; Cross-Sectional Studies ; Cryptococcosis ; immunology ; pathology ; Humans ; Lung Diseases ; immunology ; pathology ; Male ; Retrospective Studies

Bone Diseases, Infectious ; microbiology ; pathology ; Cryptococcosis ; complications ; pathology ; Forearm ; Humans ; Soft Tissue Infections ; microbiology ; pathology

Amphotericin B ; administration & dosage ; therapeutic use ; Antifungal Agents ; administration & dosage ; therapeutic use ; Biomarkers ; blood ; Child ; Cough ; diagnosis ; drug therapy ; etiology ; Cryptococcosis ; Fever ; diagnosis ; drug therapy ; etiology ; Fluconazole ; administration & dosage ; therapeutic use ; Humans ; Lung ; diagnostic imaging ; pathology ; Lung Diseases, Fungal ; complications ; diagnosis ; drug therapy ; Male ; Radiography, Thoracic ; Tomography, X-Ray Computed

OBJECTIVE: To determine the clinical characteristics, causes of pre-operative misdiagnosis and therapy of pulmonary cryptococcosis. METHODS: We retrospectively analyzed the clinical data of 28 patients suffering from pulmonary cryptococcosis from 2008 to 2013 in the Second Xiangya Hospital of Central South University. All patients were diagnosed pathologically. RESULTS: Of the 28 patients, 19 had no clear host factors. No patient was exposed to pigeons recently. The imaging findings showed that most patients had solitary, multiple nodules, masses, and patches. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed abnormal accumulation of fluorodeoxyglucose. Seven patients demonstrated malignancy and 1 demonstrated tuberculosis. None was considered as pulmonary fungus diseases. Microscopically, cryptococcosis granuloma formation was found in all patients and cryptococcosis neoformans were detected by Periodic acid-schiff and Grocott methenamine silver staining methods in the histopathological examination, respectively. Twenty-seven patients underwent lobectomy, and 1 had the medical antifungal drugs treatment. During the follow-up, symptoms in only 1 patient were not controlled. CONCLUSION Most pulmonary cryptococcosis patients have no evident immunocompromise. Clinical presentation of pulmonary cryptococcosis varies and is often related to the immune status of patients. Radiological manifestation of pulmonary cryptococcosis is indistinguishable from malignant tumor, and even 18F-FDG-PET imaging does not help to get a clear diagnosis. After surgical resection of the lung, systemic antifungal treatment is still necessary for special population. Systemic therapy of both fluconazole and itraconazole is classic choice for pulmonary cryptococcosis.
Cryptococcosis ; diagnosis ; pathology ; Fluorodeoxyglucose F18 ; Humans ; Lung ; microbiology ; pathology ; Lung Diseases, Fungal ; diagnosis ; pathology ; Positron-Emission Tomography ; Retrospective Studies ; Tomography, X-Ray Computed

We communicate the diagnosis by microscopy of a pulmonary coinfection produced by Cryptococcus neoformans and Pneumocystis jiroveci, from a respiratory secretion obtained by bronchoalveolar lavage of an AIDS patient. Our review of literature identified this coinfection as unusual presentation. Opportunistic infections associated with HIV infection are increasingly recognized. It may occur at an early stage of HIV-infection. Whereas concurrent opportunistic infections may occur, coexisting Pneumocystis jiroveci pneumonia (PCP) and disseminated cryptococcosis with cryptococcal pneumonia is uncommon. The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours and over two-thirds of patients have at least one respiratory episode during the course of their disease. Pneumonia is the leading HIV-associated infection. We present the case of a man who presented dual Pneumocystis jiroveci and cryptococcal pneumonia in a patient with HIV. Definitive diagnosis of PCP and Cryptococcus requires demonstration of these organisms in pulmonary tissues or fluid. In patients with < 200/microliter CD4-lymphocytes, a bronchoalveolar lavage should be performed. This patient was successfully treated with amphotericin B and trimethoprim sulfamethoxazole. After 1 week the patient showed clinical and radiologic improvement and was discharged 3 weeks later.
Acquired Immunodeficiency Syndrome ; complications ; Adult ; Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Bronchoalveolar Lavage Fluid ; microbiology ; Coinfection ; diagnosis ; pathology ; Cryptococcosis ; complications ; diagnosis ; pathology ; Cryptococcus neoformans ; isolation & purification ; Humans ; Male ; Microscopy ; Pneumocystis carinii ; isolation & purification ; Pneumonia, Pneumocystis ; complications ; diagnosis ; pathology ; Treatment Outcome ; Trimethoprim, Sulfamethoxazole Drug Combination ; therapeutic use

OBJECTIVETo clarify the clinical feature, diagnosis and therapy of the pulmonary cryptococcosis (PC).

METHODSA retrospective study of cases with PC who were diagnosed by pathological examinations between January 1996 and December 2010 was conducted. Eighty-one cases were enrolled in the study (58 male and 23 female patients; mean age of (51±11) years). Forty-one cases were asymptomatic at the time of diagnosis. There were single pulmonary lesions in 50 cases, and multiple lesions in 31 cases. Fourteen lesions (17.3%) were located in left upper lobe, 27 (33.3%) in left lower lobe, 21 (25.9%) in right upper lobe, 3 (3.7%) in right middle lobe, 28 (34.6%) in right lower lobe, and 3 (3.7%) diffusely involved bilateral lungs. The tumors ranged from 0.8 to 10.0 cm in diameter with a mean of (2.9±1.8) cm. All the cases were misdiagnosis prior to the surgical resection, and histologically confirmed by postoperative pathological specimens.

RESULTSAll the cases received surgical treatment including complete resection in 69 cases, and palliative resection in 12 cases. Resections were performed by means of video-assisted thoracoscopy in 31 cases and thoracotomy in 50 cases. Surgical resections included pulmonary wedge excisions in 42 cases, and lobectomies in 39 cases. After histological confirmation, 63 cases (77.8%) were treated with antifungal agents, which consisted of fluconazole in 38 cases, itraconazole in 18 cases, amphotericin B in 6 cases, and flucytosine in 4 cases. There were no intraoperative death, but two cases died for cryptococcal meningoencephalitis in the postoperative period. Operative morbidity occurred in 7 (8.6%) cases. The median follow-up was 42.5 months (6 to 84 months). There were 2 local relapses of PC, and 9 cases with complications of anti-fungal agents.

CONCLUSIONSThe clinical manifestations of PC are mild and non-specific, with no characteristic radiographic manifestations. Surgical resection is usually indicated for definite diagnosis and treatment. Antifungal drug therapy is indispensable even after complete resection.

Adult ; Aged ; Antifungal Agents ; therapeutic use ; Cryptococcosis ; diagnosis ; drug therapy ; surgery ; Female ; Follow-Up Studies ; Humans ; Lung ; microbiology ; pathology ; Lung Diseases, Fungal ; diagnosis ; drug therapy ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo study the effect of HIV-1 gp41 ectodomain (gp41-I90) on the cytoskeletal changes in human brain microvascular endothelial cells (HBMECs) induced by Cryptococcus neoformans.

METHODSHBMECs were cultured on collagen-coated chamber slide or transwell to allow the formation of cell monolayers. After pre-treatment with gp41-I90 and infection with Cryptococcus neoformans, the HBMECs were examined for the expression of actin or filamin by immunofluorescence assay. HRP permeability of the HBMECs treated with gp41-I90 was detected by ELISA. Transcytosis of Cryptococcus neoformans through the gp41-I90-treated HBMECs was detected by direct counting from a hemocytometer.

RESULTSgp41-I90 obviously enhanced the cytoskeletal changes of the HBMECs infected by Cryptococcus neoformans, causing curved and sparse filamentous arrangement of actin and filamin. gp41-I90 treatment also resulted in obviously increased HRP permeability of the cells and transcytosis of Cryptococcus neoformans.

CONCLUSIONgp41- I90 enhances Cryptococcus neoformans binding to HBMECs, which is related to its effect in enhancing Cryptococcus neoformans-induced cytoskeletal changes of the cells.

Brain ; blood supply ; Cells, Cultured ; Cryptococcosis ; pathology ; Cryptococcus neoformans ; pathogenicity ; Cytoskeleton ; drug effects ; metabolism ; Endothelial Cells ; cytology ; drug effects ; microbiology ; Endothelium, Vascular ; cytology ; drug effects ; metabolism ; HIV Envelope Protein gp41 ; pharmacology ; Humans ; Microcirculation

Aged ; Cryptococcosis ; microbiology ; pathology ; surgery ; Cryptococcus neoformans ; isolation & purification ; Follow-Up Studies ; Humans ; Laryngeal Diseases ; microbiology ; pathology ; surgery ; Male

We experienced a rare case of colonic cryptococcosis in an apparently immunocompetent individual. A 27-year- old woman admitted our hospital for intermittent melena. Initial abdominal CT scan revealed a mass lesion obstructing most of the lumen in ascending colon. Colonoscopy showed huge ulcerofungating mass in proximal ascending colon. Colonoscopic biopsy was performed and pathologic diagnosis was made as colonic cryptococcosis with positive PAS stain. Laboratory test evaluating immune status and bone marrow examination was normal. The patient was treated with intravenous amphotericin B for four weeks and six months of oral fluconazole afterwards. Follow-up abdominal CT scan and colonoscopy were taken at four weeks and seven months after the beginning of treatment. On completion of intravenous amphotericin B treatment, the mass lesion was decreased in abdominal CT and colonoscopy. After seven months, abdominal CT and colonoscopy showed near-complete resolution of the colonic lesion so the treatment ended. Cryptococcosis in a healthy individual is a rare disease and there have been only several sporadic case reports on pulmonary or central nervous system involvement. Hence, we report a case of colonic cryptococcosis in an apparently immunocompetent individual.
Adult ; Amphotericin B/therapeutic use ; Antifungal Agents/therapeutic use ; Colonic Diseases/*diagnosis/drug therapy/pathology ; Colonoscopy ; Cryptococcosis/*diagnosis/drug therapy ; *Cryptococcus neoformans ; Female ; Fluconazole/therapeutic use ; Humans ; Injections, Intravenous ; Tomography, X-Ray Computed