Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 552
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

  Table of Contents    
Year : 2022  |  Volume : 65  |  Issue : 3  |  Page : 716-718
Pleural fluid cytology in prompt diagnosis of pleuro-pulmonary nocardiosis masquerading as COVID-19

1 Department of Pathology, Father Muller Medical College, Mangalore, Karnataka, India
2 Department of Microbiology, Father Muller Medical College, Mangalore, Karnataka, India
3 Department of Internal Medicine, Father Muller Medical College, Mangalore, Karnataka, India
4 Department of Nephrology, Father Muller Medical College, Mangalore, Karnataka, India

Click here for correspondence address and email

Date of Submission23-Oct-2021
Date of Decision14-Feb-2022
Date of Acceptance04-Mar-2022
Date of Web Publication21-Jul-2022


Introduction: There are few reports of nocardial infections among the Indian population. We report this case because of its rarity and unique presentation and to highlight the role of cytology in diagnosis. Case Details: A 74-year-old woman presented with fever and chest pain of a duration of 15 days. In view of the coronavirus disease (COVID) pandemic, she was given steroids. She developed breathlessness and was referred to a tertiary care hospital. Her pleural fluid cytology showed filamentous bacteria. A diagnosis of nocardia was confirmed by culture. Discussion: Nocardiosis refers to the localized or disseminated infection caused by filamentous aerobic bacteria of the genus Nocardia. The clinical presentation of nocardiosis is highly variable. In our case, clinical misdiagnosis as COVID-19 and steroid treatment would have caused deterioration of nocardiosis. Conclusion: All patients with pulmonary symptoms should be thoroughly evaluated before considering a diagnosis of COVID-19. Pleural fluid cytology can be of help in the diagnosis of nocardiosis.

Keywords: Bacteria, cytology, infectious cytology, nocardiosis, pleural fluid

How to cite this article:
Bhat AS, Shetty AK, Bannur V, Serrao A, Bhat P, Kulkarni MJ, Joseph J. Pleural fluid cytology in prompt diagnosis of pleuro-pulmonary nocardiosis masquerading as COVID-19. Indian J Pathol Microbiol 2022;65:716-8

How to cite this URL:
Bhat AS, Shetty AK, Bannur V, Serrao A, Bhat P, Kulkarni MJ, Joseph J. Pleural fluid cytology in prompt diagnosis of pleuro-pulmonary nocardiosis masquerading as COVID-19. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Aug 15];65:716-8. Available from: https://www.ijpmonline.org/text.asp?2022/65/3/716/351588

   Introduction Top

Nocardiosis refers to the localized or disseminated infection caused by filamentous aerobic bacteria of the genus Nocardia.[1] Infection is acquired through inhalation of spores or mycelial fragments from the environment.[2] There are few reports of nocardial infections among the Indian population, with most of them in immuno-suppressed patients.[3],[xs4],[5] Pleural involvement in nocardiosis is rarely reported.[6] We report this case because of its rarity, prompt diagnosis on pleural fluid cytology, and clinical presentation mimicking COVID-19 (coronavirus disease 19) and to highlight the occurrence of nocardiosis in an immuno-competent individual.

   Case Report/Case Presentation Top

A 74-year-old woman presented with fever and chest pain of a duration of 15 days. Fever was of intermittent type and not associated with chills. The pain was mainly in the left hypochondrium, radiating to the left side of the chest. The pain increased on deep inspiration. The patient was admitted in a local hospital. In view of the COVID pandemic, she was started on steroids and antibiotics. Her reverse transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 was negative. She developed breathlessness and was referred to a tertiary care hospital. The patient is a diabetic and hypertensive and is on treatment for 15 years. On admission, her hemoglobin was 9.4 mg/dl, and her total white blood cell count was 17,100 cells/cumm with neutrophilia. The platelet count and coagulation parameters were within normal limits. The pleural fluid showed elevated adenosine deaminase of 76.2. The pleural fluid amylase, chloride, glucose, lactate dehydrogenase, and protein were within normal limits. Her chest computed tomography (CT) showed loculated pleural effusion on the left side with fibrotic changes in the left lung as shown in [Figure 1]. Pleural fluid cytology smears stained with Papanicolaou and May-Grunwald Giemsa showed filamentous bacteria in a background of a dense neutrophilic inflammatory infiltrate, as shown in [Figure 2]. Because of the presence of filamentous bacteria and cell debris, we got Ziehl–Neelson stain and modified Ziehl–Neelson stain performed. The bacteria stained faintly with Ziehl–Neelsen stain. The bacteria stained on Gram's stain and brightly with modified Ziehl–Neelsen stain using 1% sulfuric acid as a decolorizer, as shown in [Figure 3]. With this, a diagnosis of nocardiosis was made on pleural fluid cytology. Followed by this, the pleural fluid culture showed growth of nocardia species. The culture was subjected to matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry and identified as nocardia otitidiscaviarum 121106_20 HUA with a score value of 2.19 and NCBI identifier 1823. The patient was treated with the antibiotics meropenem and linezolid initially. Later, she was put on polymyxin B. The patient responded well to treatment.
Figure 1: Chest CT showing fibrotic changes in the left lung with loculated pleural effusion

Click here to view
Figure 2: May-Grunwald Stain, 1000×, showing filamentous branching bacteria

Click here to view
Figure 3: Modified acid-fast stain, 1000×, showing brightly stained acid-fast filamentous branching bacteria

Click here to view

Written informed consent to publish their case (including publication of images) and Institute Ethics Committee clearance was taken.

   Discussion/Conclusion Top

Nocardiosis was first explained by Edmond Nocard, who was a French microbiologist and veterinarian.[7] The taxonomy and speciation of Nocardia continue to evolve and are complex from a laboratory perspective.[8] At present, there are 109 published and properly named taxa of Nocardia according to the “List of prokaryotic names with standing in the literature.”[7]

The hallmark of nocardial infections is abscess formation. The protective immunity is predominantly cell-mediated. Virulent strains of Nocardia can resist killing by neutrophils directly, while some strains inhibit fusion of phagolysosome and remain as dormant L-forms which can cause relapses and severe disease.[9]

The clinical presentation of nocardiosis is variable. Pulmonary involvement can present as lung abscess, pneumonia, endobronchial mass lesion, or cavitary lesions. Empyema and pleural effusions have been reported in pulmonary nocardiosis, 90% of which are caused by Nocardia asteroids.[9] Clinical presentation may resemble lung malignancy, rhodococcal infections, or fungal infections.[2] Hence, Nocardia is described as a “great masquerader”.[8] In our case, the clinical presentation was misleading because of the pandemic of COVID-19. This led to the initiation of steroid therapy while waiting for the PCR report. This might have worsened the nocardial infection.

Pleural fluid cytology clinched the diagnosis in our case. There are very few reports describing pleural nocardiosis in the Indian population.[1],[5],[10] Among these, Nocardia was identified on pleural fluid cytology in one report,[10] as in our case. Confirmation of Nocardia infection is performed by culture. Specimens that can be submitted include bronchial washings, the bronchoalveolar lavage fluid, sputum, abscess material, aspirates, tissue biopsies, or body fluids depending on the organ involvement.[8]

In a study on fine needle aspirates from seven patients with pulmonary nocardiosis, the authors report cytomorphology showing acute and chronic inflammatory infiltrates and necrosis. None of the cases showed any granulomas. They used Gomori-methanamine silver stain and modified 1% Ziehl–Neelson stain and Gordon and sweet stain, which highlighted the delicate filamentous bacteria. The authors have concluded that fine needle aspiration cytology can provide a quick and accurate diagnosis of nocardiosis.[11] In another study on four cases of pulmonary nocardiosis, the authors describe necrosis, inflammatory cells comprising neutrophils, histiocytes, and one case with epithelioid cell granuloma.[12] In a case report on a 53-year-old man with chronic bronchitis, the authors describe filamentous nocardia-like bacteria on the bronchoalveolar lavage fluid and then confirmed Nocardia thialandica by sequencing.[13]

Long-term anti-microbial therapy is required for treatment of nocardiosis because of their slow replication and intra-cellular cryptic presence. Clinical improvement usually begins within 2 weeks of therapy initiation. Therapy needs close monitoring for assessment of response and management of drug toxicity if any develops.[8]

   Conclusion Top

Nocardiosis diagnosis requires a high index of suspicion. Pleuro-pulmonary nocardiosis can be diagnosed on pleural fluid cytology. Pleuro-pulmonary Nocardiosis can masquerade as COVID-19, and steroid therapy can worsen it. Hence, this diagnosis should be kept in mind.

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


Conflicts of interest

There are no conflicts of interest.

   References Top

Shivaprakash MR, Rao P, Mandal J, Biswal M, Gupta S, Ray P, et al. Nocardiosis in a tertiary care hospital in North India and review of patients reported from India. Mycopathologia 2007;163:267-74.  Back to cited text no. 1
Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ Jr. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev 2006;19:259-82.  Back to cited text no. 2
Singh M, Sandhu RS, Randhawa HS, Kallan BM. Prevalence of pulmonary nocardiosis in a tuberculosis hospital in Amritsar, Punjab. Indian J Chest Dis Allied Sci 2000;42:325-39.  Back to cited text no. 3
Verghese S, Kurian VM, Maria CF, Padmaja P, Elizabeth SJ, Cherian KM. Nocardia asteroides mediastinitis complicating coronary artery bypass surgery. J Assoc Physicians India 2003;51:1009-10.  Back to cited text no. 4
Gowrinath K, Das S, Ranjitham M, Sekhar U, Thanasekaraan V. Nocardial hydropneumothorax. Indian J Chest Dis Allied Sci 2004;46:51-3.  Back to cited text no. 5
Deepa R, Banu ST, Jayalakshmi G, Parveen JD. Pleuropulmonary nocardiosis due to Nocardia otitidiscaviarum in a debilitated host. Indian J Pathol Microbiol 2016;59:240-2.  Back to cited text no. 6
[PUBMED]  [Full text]  
Genus Nocardia. Available from: https://lpsn.dsmz.de/genus/nocardia. [Last accessed on 2021 Jul 21].  Back to cited text no. 7
Duggal SD, Chugh TD. Nocardiosis: A neglected disease. Med Princ Pract 2020;29:514-23.  Back to cited text no. 8
Chiang AD. Nocardia species. In: Bennett JE, Dolin R, Blaser MJ, editors. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Philadelphia: Elsevier; 2019.  Back to cited text no. 9
Bagali S, Mantur P. Pleural nocardiosis in an immunocompetent patient: A case report. J Clin Diagn Res 2016;10:DD01-2.  Back to cited text no. 10
Sood R, Tyagi R, Selhi PK, Kaur G, Kaur H, Singh A. Role of FNA and special stains in rapid cytopathological diagnosis of pulmonary nocardiosis. Acta Cytol 2018;62:178-82.  Back to cited text no. 11
Sharma S, Singh P, Garg R, Dey P. Pulmonary nocardiosis in fine-needle aspiration cytology smears: Report of four cases. Diagn Cytopathol 2016;44:347-50.  Back to cited text no. 12
Bourbour S, Keikha M, Faghri J. First report of the isolation of nocardia thailandica from the bronchoalveolar lavage of a patient in Iran. Iran J Med Sci 2018;43:560-3.  Back to cited text no. 13

Correspondence Address:
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_1036_21

Rights and Permissions


  [Figure 1], [Figure 2], [Figure 3]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

    Case Report/Case...
    Article Figures

 Article Access Statistics
    PDF Downloaded12    
    Comments [Add]    

Recommend this journal