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Year : 2020  |  Volume : 63  |  Issue : 3  |  Page : 453-455
Multiple intracranial cryptococcomas in an immunocompetent patient with pulmonary involvement

1 Department of Pathology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Radiology, Kalinga Institute of Medical Sciences and PBMH, Bhubaneswar, Odisha, India

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Date of Submission25-Apr-2019
Date of Decision30-Oct-2019
Date of Acceptance25-Nov-2019
Date of Web Publication7-Aug-2020


Opportunistic infections affecting central nervous system (CNS) have high prevalence in developing countries and cryptococcosis is one of them. It is associated with myriad of signs symptoms and clinical behavior. Though commonly associated with AIDS/HIV infection, it has been reported to be pathogenic in immunocompetent patients. Leptomeningitis is most common presentation in CNS, but unusual tumor like mass lesions have been reported. Lungs are primary site of infection, but it can affect different organs with varied clinical presentations. Therefore, correct diagnosis and proper management is essential in such cases excluding the differentials as fatality rate can be quite high. We report such an unusual case of multiple cryptococcal mass lesions in brain in a healthy immune competent individual with bilateral pulmonary involvement.

Keywords: Cryptococcosis, cryptococcoma, immunosuppression

How to cite this article:
Raman S, Mukherjee N, Dash K, Sen KK. Multiple intracranial cryptococcomas in an immunocompetent patient with pulmonary involvement. Indian J Pathol Microbiol 2020;63:453-5

How to cite this URL:
Raman S, Mukherjee N, Dash K, Sen KK. Multiple intracranial cryptococcomas in an immunocompetent patient with pulmonary involvement. Indian J Pathol Microbiol [serial online] 2020 [cited 2022 Dec 7];63:453-5. Available from:

   Introduction Top

Cryptococcus is a soil dwelling, opportunistic, capsulated yeast causing fatal disease among immune deficient humans with a mortality rate around 12%. The worldwide incidence is 0.4–1.3 per 105 population. Among the two species, Cryptococcus neoformans (CN) preferentially affects immune suppressed patients and Cryptococcus gatti (CG) is linked with immune competent individuals.[1] Though primarily localized to lungs, it may disseminate to other organs such as central nervous system (CNS), liver, spleen, kidney, and skin with diverse clinical presentations. We are reporting a case of pulmonary cryptococcosis with CNS dissemination producing uncommon multiple mass lesions in an immune competent person.

   Case Report Top

A 38-year-old male poultry farm worker presented with intermittent cough, fever, lethargy and progressively increasing weakness of right upper and lower limbs for 6 months. He showed unusual aggressive behavior since 2 months. On physical examination, he was medium built with no other physical abnormality. Further investigations revealed— Hemoglobin: 10.3 gm/dl, total leukocyte count: 19,200/cmm, total platelet count: 8.7 lac/cmm, differential leukocyte count: N85%, L12%, B00%, E02%, M01%, ESR: 73 mm/hr in Ist, sr urea: 12 mg/dl, sr creatinine: 0.5 mg/dl, sr total protein: 7.2 gm/dl, sr albumin: 3.4 gm/dl, random blood glucose: 80 mg/dl, SGOT: 29 mg/dl, SGPT: 68 mg/dl, sr alkaline phosphatase: 71 U/L, sr cholesterol: 213 mg/dl, sr triglyceride: 351 mg/dl, sr HDL: 84 mg/dl, sr VLDL: 70.2 mg/dl, sr procalcitonin: 0.54 ng/ml, HIV/HbSAg/HCV: Negative, PT: 11.9 s, INR: 1.13, aPTT: 26.4 s. Urine RE/ME revealed—protein: nil, pus cells: 16–18/hpf. CSF biochemical tests showed—glucose: 93 mg/dl, protein: 14.8 mg/dl, and adenosine deaminase: 3.00 U/L. CSF cytology revealed—normal cell count: 02/cmm and occasional lymphocytes on cytosmears. CSF gram stain, fungal stain, Indian ink preparation, and fungal culture were negative for capsulated organism or fungal elements. CSF AFB stain was negative for acid fast bacilli. Similarly, sputum gram stain and sputum culture and sensitivity (C/S) were negative. Endobronchial tube lavage fluid fungal stain showed no capsulated organism. C/S of lavage fluid, blood, and urine had no growth. Cryptococcal antigen test by latex agglutination test in serum and CSF were positive. Radiograph of the chest PA view revealed patchy nonhomogenous opacities in bilateral lung fields suggesting bilateral pneumonitis. Pulmonary Koch's or fungal infection could not be excluded [Figure 1]. Noncontrast computed tomography (NCCT) thorax revealed multiple nodules and masses in bilateral lung fields with cavitations, interlobular septal thickening in left upper lobe, and multiple calcific foci suggestive of metastasis/tuberculosis/septic pulmonary emboli [Figure 2]a and [Figure 2]b. NCCT (head/brain) and contrast-enhanced magnetic resonance imaging (CEMRI) showed cystic/cavitary lesion in right frontal, left thalamic, and left parietal region with extension to left basal ganglia, left para ventricular area, and left cerebral peduncle causing compression of left lateral ventricle [Figure 3]a. CT brain showed multiple hypodense lesions with hyperdense capsule/rim in right frontal and deep temporal lobe causing extensive mass effect and supratentorial hydrocephalus suggestive of toxoplasmosis/fungal infection [Figure 3]b and [Figure 3]c. Biopsy from brain in H and E stained sections showed multiple granulomas with Langhans and foreign body type giant cells, neutrophilic micro abscesses, and capillary proliferation. Plenty of yeast form of capsulated round to oval fungi with surrounding zone of clearing were seen in cytoplasm of giant cells [Figure 4]a. Periodic acid Schiff (PAS) and Gomori methenamine silver (GMS) stain done in the case highlighted the capsulated fungus [Figure 4]b, [Figure 4]c, [Figure 4]d. Hence, based on radiological evidence, histology, and antigen detection, a diagnosis of CNS cryptococcomas with bilateral pulmonary involvement was made. Antifungal treatment was started. On follow-up, patient is recovering slowly with residual paraparesis and intermittent headaches.
Figure 1: Chest radiograph shows bilateral nodular lung opacities

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Figure 2: (a) NCCT thorax, large spiculated cavitary lesion in superior and lateral basal segments of the right lower lobe. Few well defined small round nodules seen bilaterally. (b) NCCT thorax, right upper lobe shows a subpleural nodule with internal cavity. Left apicoposterior segments show two well-defined round smoothly marginated nodules

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Figure 3: (a) CEMRI shows cystic lesions with compression of the left lateral ventricle (arrow head). (b) T1WI images show round-shaped isointense lesions with peripheral hyper intensity exerting mass effect. (c) T2WI images show hyperintense lesion with crenated margins in frontal lobe and gangliocapsular complex compressing third ventricle

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Figure 4: Cryptococcal granuloma (arrow marked): left upper (H&E stain, 400×), Right upper (PAS stain, 400x), Left lower (GMS stain, 400x), Right lower (Gram stain, 400 x)

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   Discussion Top

Cryptococcus has four serotypes: CN: serotypes A and D and CG: serotypes B and C. CN are prevalent worldwide, whereas CG are now increasingly recognized being capable of causing disseminated disease in immune competent hosts. Human infection is acquired through inhalation of infectious spores present in bird (pigeon) droppings. Initial locus of infection is lung followed by hematogenous spread to different organs.[2] Cryptococcosis can be fatal in patients who have impaired immune status due to HIV infection, any malignancy, diabetes mellitus (DM), organ transplantation, or steroid therapy.[3]

In lungs cryptococcus induced lesions can be pneumonia, pulmonary nodules or mass lesions and pleural effusion.[3] Radiologic imaging study shows well-defined single or multiple noncalcified nodules and pulmonary infiltrates. CNS is most commonly affected by cryptococcosis in HIV patients presenting as fever, headache, lethargy, altered mental status, focal neurological deficits, increased pressure symptoms, and signs of meningeal irritation.[4] Symptoms may be acute or develop over a period of several weeks. Besides meningoencephalitis, four types of CNS mass lesions are encountered: cryptococcomas, cystic lesions alone, mixed cysts and cryptococcomas, and miliary nodules. Cryptococcoma are rare in immune competent patients. They are intraparenchymal solid tumor like masses on CT imaging and histologically granulomatous lesions containing cryptococcal organisms, lymphocytes, macrophages, and giant cells.[5] Cryptococcal cysts are formed by dilated Virchow–Robin (peri-vascular) spaces and sequestered cerebrospinal fluid. Basal ganglia and midbrain are the common sites.[6] Our case was atypical due to both pulmonary and CNS involvement, furthermore presence of pseudotumors in brain, in an immune competent host.

Cryptococci reach CNS through blood, cross the endothelial cells, and enter the CSF and perivascular spaces and then infiltrate brain parenchyma. Through inflammatory cells also they may gain entry to brain inducing chronic granulomatous reaction and cryptococcoma formation. Complications such as raised intracranial pressure, hydrocephalus, and focal neurological signs are due to blockage of CSF flow and reduced drainage of interstitial fluid.[7] The differential diagnosis of concurrent pulmonary and neurological lesions usually include tuberculosis, neurosarcoidosis, Langerhan's cell histiocytosis, toxoplasmosis, and malignancy with brain metastasis. Good clinical judgement combined with radiological, biochemical tests and histological study helps in arriving at a correct diagnosis.[8] Antifungal agent like amphotericin and surgery are the mainstay of treatment.

   Conclusion Top

A high index of clinical suspicion is necessary to diagnose cryptococcal infection in immunocompetent patients. Physician needs to be aware that all lung or brain masses are not necessarily neoplasms and treatable infection like cryptococcosis should be considered as a possibility and detailed studies must be performed to identify the causative organism.

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 b'e 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

Mirza SA, Phelan M, Rimland D, Graviss E, Hamill R, Brandt ME, et al. The changing epidemiology of cryptococcosis: An update from population-based active surveillance in 2 large metropolitan areas, 1992-2000. Clin Infect Dis 2003;36:789-94.  Back to cited text no. 1
Abid MB, De Mel S, Limei MP. Disseminated Cryptococcal infection in an immune competent host mimicking plasma cell disorder: A case report and literature review. Clin Case Rep 2015;3:319-24.  Back to cited text no. 2
Tore O, Akcaglar S, Kazak E, Heper Y, Akalin H, Hakyemez B, et al. Multiple intracranial abscesses due to cryptococcus neoformans: An unusual clinical feature in an Immune competent patient and a short review of reported cases. Med Mycol 2010;48:398-401.  Back to cited text no. 3
Maziarz EK, Perfect JR. Cryptococcosis. Infect Dis Clin North Am 2016;30:179-206.  Back to cited text no. 4
Xia S, Li X, Li H. Imaging characterization of cryptococcal meningoencephalitis. Radiol Infect Dis 2016;3:187-91.  Back to cited text no. 5
Duarte SB, Oshima MM, Mesquita JV, Nascimento FB, Azevedo PC, Reis F. Magnetic resonance imaging findings in central nervous system cryptococcosis: Comparison between immunocompetent and immunocompromised patients. Radiol Bras 2017;50:359-65.  Back to cited text no. 6
Franco- Paredes C, Chastain DB, Rodriguez Morales AJ, Marcos LA. Cryptococcal meningoencephalitis in HIV/AIDS: When to start antiretroviral therapy? Ann Clin Microbiol Antimicrob 2017;16:9.  Back to cited text no. 7
Panigrahi MK, Kumar NN, JaganathanV, Kumar SV. Pulmonary cryptococcosis with cryptococcal meningitis in an immunocompetent host. Lung India 2014;31:152-4.  Back to cited text no. 8
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Correspondence Address:
Sarojini Raman
Department of Pathology, Kalinga Institute of Medical Sciences, Campus-5, Bhubaneswar - 751 024, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_331_19

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