|Year : 2012 | Volume
| Issue : 3 | Page : 367-370
Posterior fossa midline cryptococcoma in a patient with idiopathic CD4 lymphocytopenia
S Rai1, RSK Marak2, S Jain3, TN Dhole2
1 Department of Microbiology, UCMS and GTB Hospital, Shalimar Bagh, Delhi, India
2 Department of Microbiology, SGPGIMS, Lucknow, (UP), India
3 Department of Microbiology, Max Hospital, Shalimar Bagh, Delhi, India
|Date of Submission||23-Jan-2012|
|Date of Acceptance||20-Mar-2012|
|Date of Web Publication||8-Aug-2012|
Department of Microbiology, UCMS and GTB Hospital, Shalimar Bagh, Delhi
Source of Support: None, Conflict of Interest: None
Idiopathic CD4 lymphocytopenia (ICL) is a rare disorder which is often diagnosed as HIV-negative AIDS in the light of poor immunity and AIDS-defining illnesses. We present a case of a 50-year-old male who presented with a midline posterior fossa tumour with ICL diagnosed as cerebellar cryptococcoma.
Keywords: CD4 Lymphocytopenia, posterior fossa cryptococcoma
|How to cite this article:|
Rai S, Marak R, Jain S, Dhole T N. Posterior fossa midline cryptococcoma in a patient with idiopathic CD4 lymphocytopenia. Indian J Med Microbiol 2012;30:367-70
|How to cite this URL:|
Rai S, Marak R, Jain S, Dhole T N. Posterior fossa midline cryptococcoma in a patient with idiopathic CD4 lymphocytopenia. Indian J Med Microbiol [serial online] 2012 [cited 2019 Dec 14];30:367-70. Available from: http://www.ijmm.org/text.asp?2012/30/3/367/99510
| ~ Introduction|| |
Cryptococcus neoformans is a ubiquitously present opportunistic fungus that predominantly affects HIV-infected and other immunocompromised hosts and usually involves the central nervous system either as meningitis or meningoencephalitis. The presentations may be variable depending upon the presence of other co-morbid conditions like diabetes, corticosteroid use, and immune status of the patient.  Cryptococcoma is considered to be rare in the differential diagnosis of posterior fossa masses in the paediatric population but no such correlation has been observed in adults  though similar but rare cases have been reported.  Presence of extra-pulmonary cryptococcosis is an AIDS-defining illness. We present a rare case of a midline cerebellar cryptococcoma in a patient with idiopathic CD4 lymphocytopenia (ICL) in a previously healthy adult male.
| ~ Case Report|| |
A 50-year-old male working as a clerk in a cooperative society in a rural district in eastern India, presented in the Neurology outpatient clinic in January 2009 with complaints of imbalance with staggering on either side or a tendency to fall forward for the past 1 year. He had headache initially in the posterior part of cranium, but became holocranial for the past 4 months, severe in nature and was associated with screaming. There were no aggravating or relieving factors for the headache. He also had nausea with projectile vomiting. There was history of vertigo on movement of head for the past 2-3 months.
At the commencement of the symptoms 1 year ago, the patient presented in the outpatient clinic of a tertiary care centre in 2008 with complaints of imbalance but was managed conservatively on anti-vertigo drugs. The patient had suffered from pulmonary tuberculosis almost 20 years ago for which he had taken complete successful treatment. There were no risk factors like diabetes mellitus, smoking or alcohol intake. There was no history of high risk behaviour or any multiple sexual contacts. In his native state, the patient was put on anti tubercular therapy (ATT) in October 2008 on suspicion of having a central nervous system tuberculoma. He took treatment for two and a half months, but discontinued later as there was a continuous increase in symptoms and an increase in the size of lesion seen on imaging (described later).
On examination, the patient was conscious and oriented in time, place and person and all higher functions were normal. His nutrition and build were adequate. The pupils were bilateral reacting but on fundal examination, bilateral disc margins were blurred. Visual acuity was L-6/24, R-6/18. There was no sensory or motor deficit. There was no cranial nerve deficit but cerebellar signs were positive with dysmetria and bilateral finger to nose test (FNT) being positive. He also had dysdiadokinesia (rapid alternating movements) and impaired tandem gait with an impaired right gag reflex. There was no facial asymmetry or facial numbness. Muscle power was adequate in all limbs except a weak hand grip.
Hospital course, investigations and treatment
The patient was admitted for a complete workup. Viral markers for HIV (performed by 2 different kits), HbsAg and anti-HCV were non-reactive. CD4+ counts were 174/μL and 204/μL on two separate occasions done 2 months apart. The second HIV test was done on a separate occasion (after 2 months) using a different kit in the light of a low CD4+ count. The patient was not on any immunosuppressive therapy. With negative HIV tests on multiple occasions, the patient was diagnosed as having ICL.  During the period of investigation, the total leukocyte count varied from 5 to 9.4 × 10 9 /L. The differential count demonstrated a predominance of lymphocytes approximately 40%. Due to raised intracranial pressure, lumbar puncture was deferred.
The chest X-ray was non-suggestive of any evidence of active tuberculosis. Pre-operative computer-aided tomography (CT) scans were performed which initially demonstrated large rounded heterogeneous midline enhancing lesion in posterior fossa [Figure 1] that was suspected to be a tuberculoma when the patient was put on ATT. A month later, the CT scan finding again revealed a thick irregular peripherally enhancing lesion approximately 3×3×3 cm in size, midline in posterior fossa causing compression over 4th ventricle leading to supratentorial hydrocephalus with no relieving sings due to ATT. The picture was similar even a month later. The pre-operative magnetic resonance imaging (MRI) findings, which were also done during the same time period, revealed a rounded lesion seen in the vermis measuring 3.25 × 3.18 × 3.16 cm. Another small ring enhancing area was seen just inferior to the larger lesion. The impression provided was that of a tuberculoma or a glioma [Figure 2]. No shunt-based decongestion plan was made at this stage.
|Figure 1: Pre-operative CT scan showing large rounded heterogeneous midline enhancing lesion in posterior fossa|
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|Figure 2: The pre-operative CT scan revealed a rounded lesion in the vermis. The peripheral regions are isointense to the brain parenchyma, whereas the central necrotic part is hyperintense|
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MR spectroscopy findings
Multi-voxel MR spectroscopy was performed where an area (voxel) was selected from the central part of the lesion that revealed a large lipid peak, the N-acetyl aspartate (NAA) peak was small while choline and creatinine peaks appeared to be almost absent. Another voxel selected from the peripheral part of the lesion revealed an increased choline:creatinine ratio. The NAA:Cr ratio was not reduced and lipid peaks were also seen. This was interpreted as an infective lesion [Figure 3].
|Figure 3: Multi-voxel MR spectroscopy performed from a voxel was selected from the central part of the lesion revealed a large lipid peak, small N-acetyl aspartate (NAA) peak and absent choline and creatinine. A voxel from the peripheral part of the lesion revealed increased choline:creatinine ratio. The NAA:Cr ratio is suggestive of an infective lesion|
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The patient was electively planned for sub-occipital craniotomy and decompression. The tumour was encountered at a depth of 1 cm and was soft and pale, not suckable, relatively avascular, composed of caseous material with pus in its centre. The pus was aspirated and sent for investigations to the microbiology laboratory. These findings made an intraoperative impression of that of a vermian tuberculoma.
The aspirated material sent to the microbiology laboratory was negative for any acid fast bacilli and did not have any bacterial or mycobacterial growth. On India ink wet mount microscopy, several capsulated found yeast cells with narrow based budding and numerous pus cells were seen [Figure 4]. A presumptive diagnosis of cryptococcal infection was made and the sample was subjected to fungal culture on Sabouraud Dextrose Agar (SDA) that after 3 days of incubation at 37 o C revealed small to large white creamy, pasty colonies. Gram's stain revealed budding yeast like cells which were urease positive. Growth on l-Canavanine, Glycine, 2 Bromothymol blue (CGB) agar revealed pale colonies indicating C. neoformans var neoformans. After the decompression procedure, a lumbar puncture was sent for investigation that revealed mild leucocytosis, decreased glucose levels and was positive for cryptococcal antigen test by the Calas (Meridian Bioscience) latex agglutination kit with a titre of 1:32. No fungal growth was observed in the CSF sample.
|Figure 4: India ink wet mount microscopy (×400) showing capsulated round yeast cells (a) with narrow based budding (b) and numerous pus cells|
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|Figure 5: Post-operative CT scan showing resolution and a decrease in size of the lesion after surgery and antifungal therapy|
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Post-operative course/follow up
Liposomal amphotericin B was started for fungal brain abscess along with corticosteroids which were later tapered. Potassium chloride was started as precaution for possible hypokalemia due to Amphotericin B. Repeat neuro-imaging demonstrated decreasing size of the remnant lesion [Figure 5]. After 4 weeks, Fluconazole was added and the patient began to improve clinically and headache and vomiting became passive. Ataxia and in-coordination improved. The patient had received amphotericin B in full doses of 1 mg/kg/day for 8 weeks. After this, he developed deranged renal functions and amphotericin B was stopped and creatinine was regularly monitored. Repeat CT scan that was done initially after 3 weeks of amphotericin B and after 6 weeks of full dose of amphotericin B demonstrated a decreasing size of cerebellar abscess to approximately 50% [Figure 4] but there was no complete resolution. After stopping amphotericin B, the patient was started on 5-flucytosine and oral fluconazole for 2 weeks during which there was substantial decrease in the size of remaining lesion and significant improvement in signs and symptoms. The patient was discharged on oral fluconazole with advice for follow up in outpatient clinic.
C. neoformans is the most common fungal infection affecting the nervous system and ranks third most common CNS pathology after HIV and Toxoplasmosis among pathogens causing CNS pathology. The clinical manifestations depend upon the immune status of the patient and the type of yeast infection. , In tuberculosis endemic countries like India, a tuberculoma is the usual provisional diagnosis for such CNS space occupying lesions.  However it is very rare to suspect a cryptococcoma in a patient with a negative HIV serology.  Cryptococcal infection of CNS is usually meningeal and it is rare to find parenchymal involvement. A review of 11 cases of Cryptococcosis in patients of ICL done by Zonios et al demonstrated a median CD4 count of 82 and 132 and a favourable outcome similar to this case report.  This case report emphasizes on having differential diagnosis of cryptococcoma as an important cause of cerebellar space occupying lesions in apparently healthy patients who are negative for HIV serology but may have rare immunocompromised conditions like CD4 lymphopenia.
| ~ Acknowledgment|| |
The authors would like to thank Dr AK Dixit for laboratory and logistical support.
| ~ References|| |
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
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