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Isolated bone marrow candidiasis in an immunocompetent elderly

1 Department of Pathology, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Clinical Haematology, King George's Medical University, Lucknow, Uttar Pradesh, India

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Date of Submission13-Sep-2021
Date of Decision11-Nov-2021
Date of Acceptance24-Nov-2021
Date of Web Publication13-Jan-2023

How to cite this URL:
Dubey DB, Jain M, Verma SP, Agarwal P. Isolated bone marrow candidiasis in an immunocompetent elderly. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Nov 30]. Available from:

Invasive candidiasis (IC), that is, blood stream infection with candida (candidemia) and deep-seated infection usually occur in immunocompromised hosts with identifiable risk factors namely diabetes mellitus, haemodialysis, post-transplant, chemotherapy, HIV, severe neutropenia and broad-spectrum antibiotic or steroid therapy. IC is rare in an immunocompetent host.

A 72-year-old male presented with generalised weakness and pallor for 8 months. His systemic examination was unremarkable. He had no history of fever, any chronic illness, comorbidity, substance abuse, surgical intervention, nor prolonged drug intake (including steroids, antibiotics). His complete blood count (CBC) showed moderate anaemia (Hb 9.4 gm/dl) with presence of macrocytic cells, thrombocytopenia (63 × 109/L), and mild neutropenia (1.41 × 109/L). Serum iron profile and vitamin B12 showed adequate stores. Biochemical tests for serum protein, serum albumin, liver function, renal function. lactate dehydrogenase levels, and HbA1C were within normal limits. Serology for viral markers of HIV, Hepatitis B surface antigen, Anti-Hepatitis C virus antibody were negative. Bone marrow smears were normocellular with relative increase in erythroid precursors. No increase in blast count, left shift or significant dysplasia was seen. A normal karyotype was seen in the bone marrow sample. The trephine biopsy had 10 intertrabecular spaces of which one showed obliteration of marrow space by budding yeast forms and septate pseudohyphae with adjoining areas of necrosis. The hyphae were positive for Periodic Acid Schiff (PAS) stain [Figure 1]a, [Figure 1]b, [Figure 1]c. The morphology of cellular areas were consistent with aspirate findings. A diagnosis of isolated marrow mycosis with Candida species was given. The bone marrow aspirate culture was not done as the diagnosis was not suspected initially. The blood culture analysis for fungus was negative. A possibility of skin contamination was ruled out as the site of biopsy was sterilized as per standard protocol before the procedure and biopsy was fixed immediately. Also the skin examination was unremarkable.
Figure 1: (a and b) Bone marrow trephine biopsy showing intertrabecular space with septate pseudo hyphae, budding yeast forms, blastopores with adjoining necrosis (Haematoxylin and Eosin stain a: 400x, b: 630X). (c) Periodic acid Schiff positive hyphae (400X)

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After the confirmation of marrow mycosis, patient was started on fluconazole 400 mg once daily for 2 weeks. A follow-up CBC showed response in all three lineages (Hb 9.8 gm/dl, ANC 3.3 × 109/L, PC 248 × 109/L).

Isolated bone marrow mycosis in an immunocompetent host without evidence of fungemia or septicaemia is rarely reported.[1] An elderly male having macrocytic anaemia, thrombocytopenia, and mild neutropenia with adequate nutritional reserves suggested an underlying marrow involvement in form of neoplastic or dysplastic proliferation of hematopoietic precursors. The bone marrow mycosis was not clinically suspected. An obvious portal of entry may not be evident as in the present case.[2] It's difficult to diagnose IC in an immunocompetent patient as 50--70% of the general population is naturally colonized by this organism. Neutrophil-driven cell-mediated immunity with IL-1 and IL-17 acts as a protective barriers against these colonials.[3]

The gold standard for diagnosing IC is blood culture. The sensitivity as reported in autopsy proven cases of IC varies from 21 to 71% depending on sampling frequency and the amount of blood drawn.[4] Deep-seated candidiasis results from progression of approximately 50% primary candidemia cases. As the window of opportunity for positive culture is narrow, active candidemia is generally missed, and only about 40% of these cases yield a positive blood culture. For blood culture-negative cases, histopathology with special stains or culture from the site of involvement is diagnostic.[4],[5] PAS and Grocott-Gomori Methenamine silver stain recognises carbohydrate in fungal cell wall. In the present case, tissue culture could not be done as the biopsy was formalin fixed. Prognosis for IC is very poor with mortality rate as high as 40% regardless of therapy.

The present case highlights the role of trephine biopsy in diagnosing a clinically unexpected treatable infectious cause of cytopenia in an elderly male.

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.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Zimpfer A, Piehler P, Kofler G, Dirnhofer S, Tzankov A. Isolated bone marrow mycosis in a patient presenting with consumptive symptoms. J Clin Pathol 2004;57:107-8.  Back to cited text no. 1
Diebold J, Molina T, Camilleri-Broët S, Le Tourneau A, Audouin J. Bone marrow manifestations of infections and systemic diseases observed in bone marrow trephine biopsy review. Histopathology 2000;37:199-211.  Back to cited text no. 2
Altmeier S, Toska A, Sparber F, Teijeira A, Halin C, LeibundGut-Landmann S. IL-1 coordinates the neutrophil response to C. albicans in the oral mucosa. PLoS Pathog 2016;12:e1005882.  Back to cited text no. 3
Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis. Nat Rev Dis Primers 2018;4:18026.  Back to cited text no. 4
Ericson EL, Klingspor L, Ullberg M, Ozenci V. Clinical comparison of the Bactec Mycosis IC/F, BacT/Alert FA, and BacT/Alert FN blood culture vials for the detection of candidemia. Diagn Microbiol Infect Dis 2012;73:153-6.  Back to cited text no. 5

Correspondence Address:
Mili Jain,
Department of Pathology, King George's Medical University, Lucknow, Uttar Pradesh - 226 003
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_918_21


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