Clinical presentation of cerebral cryptococcal granuloma mimics brain tumour which confounds the diagnosis. Granuloma formation is rare. Two varieties and five serotypes have been recognised, viz., C. neoformans var neoformans serotypes (A, D, AD) and C. neoformans var gattii (B, C). C. neoformans is more likely to cause disease in immunocompromised hosts, whereas C. gattii is implicated in immuonocompetent ones [10, 11]. The variety in our patient was C. neoformans. However, further serotyping was not done as it was not available at our institute. Cryptococcoma formation is more common with C. gattii [12]. Clinical features of brain involvement are nonspecific. Raised intracranial tension features characterised by headache, vomiting and later on focal neurological deficit may be seen depending upon the location of the granuloma which was in the form of dysphasia in our patient.
Sparse literature is available about similar cases. Nadkarni et al. [13] reported a case of a 22-year-old patient who presented with focal seizures with secondary generalization. Imaging revealed a peripheral ring-enhancing lesion in the left parietal lobe with significant edema. He was started on anti-tubercular regimen and anticonvulsants to which he initially seemed to respond only to have repeat seizures a year later. Repeat imaging revealed increase in edema, and the patient underwent a stereotactic biopsy finally revealing the diagnosis of cryptococcosis. Like in our patient, the diagnosis of cryptococcosis was made only after histopathology and the more common pathology, viz., metastasis in our case and tubercular granuloma in this case were considered first. More importantly, the workup for HIV was negative in both patients.
Qi Zhu et al. [14] reported a case of a 12-month-old child with 6-month history of seizures. Initial workup for seizures revealed bilateral EEG slow wave activity especially in the left occipital region. CT showed irregularly calcified lesion in left parieto-occipital region. MRI demonstrated mixed signals without edema or visible flow voids. It was diagnosed as a vascular malformation. Three years later, when she presented with increased frequency of seizures and underwent an excision of the lesion, it was revealed to be cryptococcal granuloma. This case reinforces the status of cryptococcal granuloma as a great mimic.
Li et al. [15] in 2009 while reviewing the available 17 cases in literature reported their own case of a 49-year-old woman who was clinico-radiologically diagnosed with high grade glioma of the right occipital lobe. Similar to our case, she did not have any meningeal signs, had focal deficit in the form of right homonymous hemianopia and was afebrile. Workup for immune compromise status was negative. However, unlike our case, CSF in her case did not reveal any cryptococci.
Gologorsky et al. [16] reported an African American 12-year-old whose clinical presentation was suggestive of cerebellar lesion and CT and MRI showed ring-enhancing right cerebellar lesion suggestive of cerebellar astrocytoma. Excision of lesion revealed it to be cryptococcal granuloma. However, unlike our patient, the child had been febrile at presentation with a fever of 100.9°F. Similar to our patient, he did not have any papilledema. CT features include hypodense or isodense mass with homogenous and ring-like enhancement after contrast injection. At times, the granuloma may be calcified on CT [14]. MRI is the most sensitive modality for diagnosis of the nature of mass lesion. However, in this case, it offers a large gamut of differentials including metastatic malignancy, lymphoma, toxoplasmosis, tuberculoma, pyogenic abscess and primary CNS malignancy [15, 16]. On MRI, the lesions appear low intensity on T1WI (T1 weighed imaging) and high intensity on T2WI (T2 weighed imaging). On DWI (diffusion weighed imaging), hypointensity in the central cavity mimics a necrotic brain tumour rather a pyogenic abscess. Contrast enhancement is uncommon in immunocompromised patients due to the underlying immunosuppression and non-immunogenic nature of the polysaccharide capsule of the organism [17]. This is well described by Kamezawa et al. [18] in their case in which the CT scan revealed a cystic lesion abutting the right frontal horn. Further evaluation with MRI had suggested a lesion mimicking the CSF intensities on both T1 and T2 images without contrast enhancement. However, the DW-EPI and FLAIR gave a higher signal and a more heterogenous signal on DWI leading to a diagnosis of epidermoid. However, our patient showed contrast enhancement. Taneja et al. had reported a case similar to ours which had presented with raised ICP features, hemiparesis and fever. Imaging had revealed multiple ring-enhancing lesions and CSF had yielded C. neoformans [19]. However, their experience was different from ours in having features of meningitis which prompted them to carry out CSF investigations. Our patient had only raised ICP features and expressive dysphasia with no meningeal signs.
Spectroscopy shows increased lactate along with decrease in NAA (N-acetyl aspartate) suggesting neuronal damage. However, this is a non-specific sign. In their study describing the MRS characteristics of cerebral abscesses of differing aetiologies, Dusak et al. noted the presence of succinate, alanine, lipid and lactate [20]. Histopathology showed characteristic features of a fungal granuloma which consisted mainly of numerous encapsulated fungal spores, lymphocytes, eosinophilic granulocytes, neutrophilic granulocytes, fibroblasts, multinucleated giant cells and multiple calcifications.
Medical management of cerebral cryptococcosis relies upon the use of one of the available form of intravenous amphotericin B and 5-FC for induction followed by consolidation and maintenance with fluconazole [21]. Surgery is necessary for a definitive diagnosis and therapy especially in cases presenting with mass effect. Post-operatively, anti-fungal drugs are used to prevent cryptococcal meningitis [22]. Surgery may also shorten the duration of anti-fungal treatment [23].
