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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 9  |  Issue : 4  |  Page : 457-460

Positive (1,3)-β-D-Glucan and Galactomannan in a 73-Year-Old Male with Lung Adenocarcinoma


Department of Clinical Pathology, Faculty of Medicine, Saiful Anwar General Hospital, Brawijaya University, Malang, Indonesia

Date of Submission29-Sep-2020
Date of Decision14-Nov-2020
Date of Acceptance18-Oct-2020
Date of Web Publication15-Dec-2020

Correspondence Address:
Lydiana Parmadi
Department of Clinical Pathology, Faculty of Medicine, Saiful Anwar General Hospital, Brawijaya University, Malang
Indonesia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_181_20

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  Abstract 


Invasive pulmonary aspergillosis (IPA) is a life-threatening condition. Patients with lung cancer 73.9% died within 1 month after IPA diagnosis. Diagnosing IPA is challenging because of the nonspecific clinical symptoms, radiological findings, lack of sensitivity, and need time in culture method. A 73-year-old male presented with shortness of breath, productive cough, fever, chest pain, and a decrease of body weight. On right thorax auscultation, decreased of vesicular breath sound, rhonchi, and pleural friction rub were found. The chest radiograph revealed a right lung tumor. We confirmed the existence of Aspergillosis on the fiberoptic bronchoscopy (FOB) result by conducting the serology examination (1,3-β-D-glucan and Galactomannan) using the enzyme-linked immunosorbent assay method. Bronchoalveolar lavage culture from FOB result was Aspergillus fumigatus, and fine-needle aspiration biopsy showed adenocarcinoma. Because IPA is a life-threatening condition, an early diagnosis is important. Therefore, a serology test is necessary for the early detection of suspected case of fungal infection and useful to complement the culture.

Keywords: 1, 3-β-D-glucan, Galactomannan, invasive pulmonary aspergillosis


How to cite this article:
Parmadi L, Ginting IM, Susianti H. Positive (1,3)-β-D-Glucan and Galactomannan in a 73-Year-Old Male with Lung Adenocarcinoma. Int J Mycobacteriol 2020;9:457-60

How to cite this URL:
Parmadi L, Ginting IM, Susianti H. Positive (1,3)-β-D-Glucan and Galactomannan in a 73-Year-Old Male with Lung Adenocarcinoma. Int J Mycobacteriol [serial online] 2020 [cited 2021 Jan 22];9:457-60. Available from: https://www.ijmyco.org/text.asp?2020/9/4/457/303452




  Introduction Top


Aspergillus spp. is one species of opportunistic pathogenic fungi.[1] This fungus can be found in soil, dust, food, and rotten matter. Aspergillus spores can enter through inhalation into the lungs or orally through contaminated food or water. Aspergillus does not cause clinical manifestations in immunocompetent individuals. However, immunocompromised patients can cause life-threatening diseases. This condition is called invasive pulmonary aspergillosis (IPA).[2],[3] A study conducted by Yan et al. mentions that 23 out of 45 patients (51.1%) died due to IPA infection and 17 of the 23 patients (73.9%) died within 1 month after being diagnosed with IPA.[4]

Epidemiology of invasive aspergillosis (IA) in the world is estimated at around 200,000 cases per year. At present, about 50% of all IA is found in patients with hematological malignancies and posttransplant patients. Patients with severe neutropenia (<500 cells/mm3) and prolonged duration (>10 days) caused by chemotherapy or immunosuppressant therapy are the risk factors for IA.[3] The risk of IPA in patients with hematological malignancies is well-known, but the incidence of lung cancer is rarely diagnosed because it has no distinctive symptoms, nonspecific radiological features, and fungal culture which takes a long time and has a low sensitivity. The following is a case of IPA in patients with pulmonary adenocarcinoma. In this case, a positive result was obtained from the enzyme-linked immunosorbent assay (ELISA) serological examination and fungal culture obtained from bronchoalveolar lavage (BAL) sample. We report this case because it is a rare and difficult case in the diagnosis process. Early diagnosis can help provide faster management for a better prognosis.


  Case Report Top


A 73-year-old male comes with the main complaint of shortness of breath for 1 month before entering the hospital. Complaints accompanied by coughing with thick white phlegm and sometimes accompanied by blood. This complaint is especially felt when walking and improves when resting. Complaints are also accompanied by chest pain, fever that occurs, and weight loss within 1 month. The patient is a retired soldier. History of smoking habits 1 pack per day.

On physical examination found a general state of moderate, compos mentis awareness, blood pressure 130/80 mmHg, pulse frequency 110x/min, respiratory frequency 28x/min, temperature 36.9°C, and nutritional status is poor. In the thorax examination found 1 and 2 single heart sounds, there are no murmurs or gallop; right lungs decreased breathing sounds, rhonchi, and pleural friction rub. Examination of the abdomen and extremities is within the normal limits.

Laboratory examination

The serology examination was performed on the same day with other examination including BAL culture; the result was completed within 6 h. Laboratory examination shows [Table 1],[Table 2],[Table 3],[Table 4],[Table 5],[Table 6]
Table 1: Complete blood count

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Table 2: Coagulation test

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Table 3: Biochemistry

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Table 4: Electrolyte serum

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Table 5: Immunoserology

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Table 6: Fungal serology

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Radiological examination results showed a picture of the right lung tumor [Figure 1]. Bronchoscopy examination revealed obstruction with intra-lumen mass in the superior lobe of the right bronchus [Figure 2]. Then, biopsy and washing were done as well as BAL. Histopathological examination with fine-needle aspiration biopsy gives a figure of pulmonary adenocarcinoma. Examination of the epidermal growth factor receptor mutation detected mutations in exon 21.
Figure 1: Chest radiograph shows a right lung tumor

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Figure 2: Obstructive bronchoscopy with intra lumen mass in the superior lobe of the right bronchus

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BAL sample was cultured using Sabouraud dextrose agar and Aspergillus fumigatus [Figure 3] was detected after 21 days.
Figure 3: (a) Bronchoalveolar lavage culture (1) Microsporum audouinii; (2) Aspergillus fumigatus; (3) contaminants; (4) Microsporum audouinii. (b) Microscopic hyphae with septa, round conidia, greenish color

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  Discussion Top


IPA is a life-threatening condition in immunocompromised patients. Based on radiology and histopathology results, the patient was diagnosed with pulmonary adenocarcinoma. The patient has a low CD4 cell count which is an immunocompromised state. The results of culture with BAL samples found A. fumigatus. The diagnosis of IPA is quite difficult because of the low sensitivity of the culture method and requires a long time. Nonculture based tests offer a faster diagnosis, but nonculture based tests are also said to be less sensitive.[5] Nonculture-based tests detect fungal antigens such as 1,3-β-D-Glucan (BDG) and Galactomannan (GM).

The fungus has a cell wall consisting mainly of polysaccharides (glucan, mannan) and chitin.[6] BDG is a cell wall polysaccharide in most fungal pathogens except for a few species of Cryptococcus, Mucoromycotina, and Basidiomycota so BDG is not specific for the diagnosis IA.[7],[8] GM is antigen containing polysaccharides, located in the outer layer of Aspergillus cell walls and because of its location on the surface, this allows GM to cover other polysaccharides such as BDG.[9] GM is the only polysaccharide antigen characterized in A. fumigatus.[10]

The gold standard for diagnosing aspergillosis based of culture or histopathology which must be done with sterile sample conditions and takes a long time. Even though, the culture provided high specificity on fungal infection, it only provided <50% sensitivity.[8]

The method used in the BDG and GM examination is a sandwich ELISA using human monoclonal antibodies. GM and BDG examination can use serum samples or other body fluids such as BAL and cerebrospinal fluid. In this case the sample used is BAL fluid. Several studies have suggested that sensitivity and specificity using BAL fluid samples are higher than serum.[7],[11] In several studies and two meta-analysis studies, GM performance on BAL fluid samples showed a sensitivity of 85%–90% and specificity of 90%–95%, whereas sensitivity in serum samples is 60%–80% with specificity of 80%–90%.[7] The recommended GM cut-off value is optical density >0.5. Nonneutropenic patients with IPA who often show negative results in serum because GM is secreted directly on the respiratory tract, the detection of GM in BAL fluid will be very helpful in establishing diagnosis.[8] According to the BDG study on BAL samples conducted by Atalay et al., sensitivity was 93.3%, specificity was 53.3%, positive predictive value 50%, negative predictive value 94.1%, at a cutoff of 80 pg/mL.

Based on complaints, clinical manifestations, and investigations, the patient was diagnosed with IPA in pulmonary adenocarcinoma. The culture examination takes a long time until the results are obtained. GM and BDG serological tests can give earlier results before culture results are obtained so that they can be used to help diagnose early.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tille PM, editor. Bailey & Scott's Diagnostic Microbiology. 13th ed. St. Louis, Missouri: Elsevier Inc.; 2014. p. 741-5.  Back to cited text no. 1
    
2.
Naaraayan A, Kavian R, Lederman J, Basak P, Jesmajian S. Invasive pulmonary aspergillosis-case report and review of literature. J Community Hosp Intern Med Perspect 2015;1:3-6.  Back to cited text no. 2
    
3.
Schmiedel Y, Zimmerli S. Common invasive fungal diseases: An overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia. Swiss Med Wkly 2016;146:w14281.  Back to cited text no. 3
    
4.
Yan X, Li M, Jiang M, Zou LQ, Luo F, Jiang Y. Clinical characteristics of 45 patients with invasive pulmonary aspergillosis: Retrospective analysis of 1711 lung cancer cases. Cancer 2009;115:5018-25.  Back to cited text no. 4
    
5.
Kauffman C, Pappas P, Sobel J, Dismukes W. Essentials of Clinical Mycology. 2nd ed. NY: Springer New York; 2011.  Back to cited text no. 5
    
6.
Ryan KJ, editor. Sherris Medical Microbiology. 7th ed. United States: McGraw-Hill Education; 2018. p. 778-81.  Back to cited text no. 6
    
7.
Lamoth F. Galactomannan and 1,3-β-d-Glucan Testing for the Diagnosis of Invasive Aspergillosis. J Fungi 2016;2:22.  Back to cited text no. 7
    
8.
Mikulska M, Furfaro E, Viscoli C. Non-cultural methods for the diagnosis of invasive fungal disease. Expert Rev Anti Infect Ther 2015;13:103-17.  Back to cited text no. 8
    
9.
Barreto-Bergter E, Figueiredo RT. Fungal glycans and the innate immune recognition. Front Cell Infect Microbiol 2014;4:145.  Back to cited text no. 9
    
10.
Thornton CR. Detection of Invasive Aspergillosis. Advances in Applied Microbiology. Vol. 70. 1st ed. United States: Elsevier Inc.; 2010. p. 187-216. Available from: http://dx.doi.org/10.1016/S0065-2164 (10) 70006-X. [Last accessed on 2019 August 1].  Back to cited text no. 10
    
11.
Lahmer T, Neuenhahn M, Held J, Rasch S, Schmid RM, Huber W. Comparison of 1,3-β-D-glucan with galactomannan in serum and bronchoalveolar fluid for the detection of Aspergillus species in immunosuppressed mechanical ventilated critically ill patients. J Crit Care 2016;36:259-64. Available from: http://dx.doi.org/100.1016/j.jcrc. 2016.06.026. [Last accessed on 2019 August 1].  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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