This article is a commentary on:
Comparison of different therapeutic approaches for pulmonary cryptococcosis in kidney transplant recipients: a 15-year retrospective analysis
Lei Gu
Jing Lin4†- 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China
- 2Institute of Respiratory Diseases, Soochow University, Suzhou, China
- 3Suzhou Key Laboratory for Respiratory Diseases, Suzhou, China
- 4Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- 5Department of Respiratory and Critical Care Medicine, The 900th Hospital of Joint Logistic Support Force, People's Liberation Army, Fujian Medical University, Fuzhou, Fujian, China
- 6The People's Hospital of Gaozhou, Gaozhou, China
A Commentary on
Comparison of different therapeutic approaches for pulmonary cryptococcosis in kidney transplant recipients: a 15-year retrospective analysis
by Chen, S., Yu, G., Chen, M., You, Y., Gu, L., Wang, Q., Wang, H., Lai, G., Yu, Z., and Wen, W. (2023). Front. Med. 10:1107330. doi: 10.3389/fmed.2023.1107330
We read with great interest the article by Chen et al. (1) published in Front. Med. (Lausanne). The remarkable discovery of this study is that patients with pulmonary cryptococcosis (PC) often received surgical resection as a therapeutic approach (39.13%, 9/23) because PC frequently manifested nodule-shaped lesions, which closely resemble lung carcinoma. In a prospective multi-center clinical study of HIV-negative PC in China, the majority of the patients were devoid of underlying diseases (70.24%, 321/457) and were immunocompetent (87.75%, 401/457), and 25.16% (115/457) of the patients had no clinical symptom or physical signs (2). Compared with immunocompromised patients, 57.14% of immunocompetent patients were asymptomatic (3). The chest computed tomography (CT) scans revealed that the majority of PC lesions presented as solitary or multiple nodules, constituting 51.54% middle-sized nodules (ranging from 1 to 5 cm), 28.07% small-sized nodules (ranging from 3 mm to 1 cm) (2), and 10.09% nodular masses exceeding 5 cm (4). These intricate presentations often give rise to a diagnostic challenge, with cases frequently being initially misinterpreted as instances of lung cancer. The misdiagnosis rate of PC during the initial visit was even 43.42% (33/76), often as cancer by false-positive 18 FDG-PET (28 out of 46 cases) (5). Therefore, early diagnosis of nodular or mass PC remains crucial, which can not only avoid misdiagnosis and unwarranted surgical procedures but also reduce potential harm to patients and healthcare costs.
Currently, diagnosis of PC mainly relies on histopathological examinations (74.40%, 340/457) and cryptococcus antigen (CrAg) detection (37.64%, 172/457) (2). Of course, smears and cultures of cryptococcus in respiratory samples, such as sputum or bronchoalveolar lavage fluid (BALF), are also important diagnostic methods. However, the proportion of cases that can be confirmed by smears and cultures of cryptococcus is extremely low. Due to the invasive nature of percutaneous lung biopsy and the difficulty in biopsying some pulmonary nodules, the histopathological diagnosis of PC is limited, which often leads to missed diagnoses and misdiagnoses, causing unwarranted surgical operations. CrAg detection has become an important method for the clinical diagnosis of PC. In HIV-negative PC patients, the sensitivity of the serum CrAg test was 71.99% (203/282) (2). The sensitivity of serum CrAg was higher in HIV patients with PC (6). A meta-analysis evaluated the diagnostic accuracy of the CrAg lateral flow immunoassay (LFA) on serum and found that the pooled sensitivity and specificity values of LFA in serum were 97.6 and 98.1%, respectively (7). Zhu et al. (8) reported that the diagnostic performance of BALF CrAg-LFA for PC was notable, demonstrating a sensitivity of 93.9% (31/33), a specificity of 100% (78/78), and an accuracy of 98.2%, which was superior to the diagnostic value of serum CrAg-LFA. Zeng et al. (9) also found that the sensitivity and specificity of serum CrAg-LFA were 75.0 and 99.6%, respectively, while those of BALF were 93.1 and 100%, respectively. The LFA is a point-of-care test that requires no specimen preparation. It has become the recommended test due to its lower cost and ease of testing. However, the positive rate of CrAg in immunocompetent hosts was lower than that in immunocompromised hosts, and a negative test result could not exclude PC, especially for normal immune function patients.
To sum up, we urge clinicians to consider nodular PC in the differential diagnosis of pulmonary nodules and masses. Clinicians should improve their knowledge of PC imaging features and increase their understanding and attention to the disease, and serum or BALF CrAg screening should be performed in patients who cannot be excluded from PC first.
Author contributions
WL: Visualization, Writing—review and editing. LG: Writing—original draft. JL: Writing—original draft. JY: Conceptualization, Validation, Writing—review and editing. J-aH: Writing—review and editing.
Funding
This research was supported by the National Natural Science Foundation of Fujian Province, China (No. 2020J011129).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
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References
1. Chen S, Yu G, Chen M, You Y, Gu L, Wang Q, et al. Comparison of different therapeutic approaches for pulmonary cryptococcosis in kidney transplant recipients: a 15-year retrospective analysis. Front Med. (2023) 10:1107330. doi: 10.3389/fmed.2023.1107330
2. Chen LA, She DY, Liang ZX, Liang LL, Chen RC, Ye F, et al. A prospective multi-center clinical investigation of HIV-negative pulmonary cryptococcosis in China. Chin J Tubercul Respir Dis. (2021) 44:14–27. doi: 10.3760/cma.j.cn112147-20200122-00034
3. Wang DX, Zhang Q, Wen QT, Ding GX, Wang YG, Du FX, et al. Comparison of CT findings and histopathological characteristics of pulmonary cryptococcosis in immunocompetent and immunocompromised patients. Sci Rep. (2022) 12:5712. doi: 10.1038/s41598-022-09794-6
4. Liu K, Ding H, Xu B, You R, Xing Z, Chen J, et al. Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary cryptococcosis. J Thorac Dis. (2016) 8:2813–21. doi: 10.21037/jtd.2016.10.36
5. Zhang Y, Li N, Zhang Y, Li H, Chen X, Wang S, et al. Clinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis. Eur Respir J. (2012) 40:1191–200. doi: 10.1183/09031936.00168011
6. Hevey MA, George IA, Rauseo AM, Larson L, Powderly W, Spec A. Performance of the lateral flow assay and the latex agglutination serum cryptococcal antigen test in cryptococcal disease in patients with and without HIV. J Clin Microbiol. (2020) 58:e01563–20. doi: 10.1128/JCM.01563-20
7. Huang HR, Fan LC, Rajbanshi B, Xu JF. Evaluation of a new cryptococcal antigen lateral flow immunoassay in serum, cerebrospinal fluid and urine for the diagnosis of cryptococcosis: a meta-analysis and systematic review. PLoS ONE. (2015) 10:e0127117. doi: 10.1371/journal.pone.0127117
8. Zhu N, Lin S, Weng X, Sun W, Chen X. Performance of the colloidal gold immunochromatography of cryptococcal antigen on bronchoalveolar lavage fluid for the diagnosis of pulmonary cryptococcosis. Can J Infect Dis Med Microbiol. (2022) 2022:7876030. doi: 10.1155/2022/7876030
9. Zeng HQ, Zhang XB, Cai XY, Yang DY, Lin L, Chen MJ, et al. Diagnostic value of bronchoalveolar lavage fluid cryptococcal antigen-lateral flow immunochromatographic assay for pulmonary cryptococcosis in non-HIV patients. Diagn Microbiol Infect Dis. (2021) 99:115276. doi: 10.1016/j.diagmicrobio.2020.115276
Keywords: pulmonary cryptococcosis, pulmonary nodules, lung cancer, cryptococcus antigen, nodule
Citation: Gu L, Lin J, Liu W, Yue J and Huang J-a (2023) Commentary: Comparison of different therapeutic approaches for pulmonary cryptococcosis in kidney transplant recipients: a 15-year retrospective analysis. Front. Med. 10:1275042. doi: 10.3389/fmed.2023.1275042
Received: 09 August 2023; Accepted: 28 September 2023;
Published: 17 October 2023.
Edited by:
Roberto Carbone, University of Genoa, ItalyReviewed by:
Sebastien Imbert, Université de Bordeaux, FranceCopyright © 2023 Gu, Lin, Liu, Yue and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jian-an Huang, huang_jian_an@163.com; Jian Yue, tamoxifen@126.com
†These authors have contributed equally to this work