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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 58, Num. 2, 2010, pp. 300-302

Neurology India, Vol. 58, No. 2, March-April, 2010, pp. 300-302

Case Report

Cryptococcal osteomyelitis of the skull in a patient with transient lymphopenia

Department of Neurology and Medicine, Bangalore Medical College and Research Institute, Bangalore, India

Correspondence Address: J B Agadi, Department of Neurology, Bowring & Lady Curzon Hospitals, Bangalore Medical College & Research Institute, Bangalore, India,

Date of Acceptance: 02-Nov-2009

Code Number: ni10075

PMID: 20508355

DOI: 10.4103/0028-3886.63798


Cryptococcus neoformans is a rarely reported cause for osteomyelitis. We report an extremely unusual case of calvarial cryptococcal osteomyelitis in a 42-year-old sub-optimally immunocompetent male. This case discusses the atypical presentations of cryptococcosis in HIV-negative patients and its importance of early diagnosis.

Keywords: Calvarial, cryptococcal osteomyelitis, renal cell carcinoma, transient lymphopenia


Cryptococcosis is the most common fungal infection of the central nervous system (CNS), especially in immunocompromised individuals and Cryptococcus neoformans is the common pathogen. [1] Resistance to cryptococcosis depends primarily on cell-mediated immunity. The typical pathology of CNS cryptococcosis include meningitis, cryptococcomas, and dilated perivascular spaces from spread of the organism. Skeletal cryptococcal infections is extremely rare. The most common site of bone involvement is lumbar spine, pelvis and ribs.

Case Report

A 42-year-old male presented with a two-month history of right frontal headache and vomiting since three days. His past medical history was significant for diabetes mellitus and hypertension, both of which were under control with treatment. He was on treatment for tuberculosis of left knee joint since three months. He also had sequelae of childhood paralytic polio. There was no history of any high-risk behavior. He was afebrile and neurological examination showed neck stiffness and Kernig′s sign and no focal deficits. Ocular fundi were normal. He had a 3 x 3 cm swelling on the right frontal bone. Left knee joint showed no evidence of arthritis. His laboratory investigations and chest X-ray were essentially normal. He was negative for HIV 1 and 2. A computed tomography (CT) scan of the head showed a solitary lytic lesion in the inner table of skull vault in the right frontal region [Figure - 1].

A biopsy of the lesion yielded only thick pus-like fluid, which was sent for culture. A CSF examination revealed clear and colorless fluid with elevated protein levels. His CSF leukocyte count was elevated (400 cells/mm 3 ) with 100% lymphocytes. CSF India ink, ZN staining and VDRL were negative. A culture from the CSF showed Cryptococcus neoformans. The culture of the frontal bone biopsy specimen also yielded Cryptococcus neoformans. He was started on antifungal treatment. His repeat testing for HIV including nucleic acid test for HIV-1 was negative. A CD4 count was done to check for any immunodeficiency and was found to be low (226 cells/mm 3 ). Serum protein electrophoresis revealed a normal pattern with immunoglobulin levels within normal limits. A CT scan of the thorax showed no evidence of pulmonary cryptococcosis. However, a CT of the abdomen showed a well-defined heterogeneously enhancing exophytic mass lesion arising from the antero-infero-medial aspect of the right kidney with areas of necrosis [Figure - 2]. A CT guided FNAC of the renal mass showed benign epithelial cells with scattered areas of necrosis and hemorrhage. A possibility of renal cryptococcosis or a malignant lesion was considered and an urologist opinion was sought. A right radical nephrectomy was done as the possibility of renal cell carcinoma could not be ruled out in entirety and the histopathology of the specimen showed a clear cell carcinoma grade I and II with a tumor embolus in the renal vein.

His repeat CSF culture was negative for cryptococci done twice at second and sixth week of treatment. His repeat CD4 counts were within normal limits. He was discharged with oral fluconazole for 10 weeks.


Cryptococcus neoformans is a budding yeast found throughout the world in soil, milk, wood, and avian feces. The mode of cryptococcal transmission to human beings is believed to be through inhalation of aerosolized droppings, which cause asymptomatic pulmonary granulomata in immunocompetent patients. Dissemination of Cryptococcus is seen in immunocompromised patients, with a predilection for the central nervous system.

Cryptococcus neoformans infection is common in immunocompromised patients, especially in patients with AIDS. [1] Over the last decade, cases of low CD4+ T-lymphocyte counts in the absence of HIV infection have been reported. [2] A syndrome called Idiopathic CD4+ T Lymphocytopenia (ICL), was recognized in 1992 that was characterized by an absolute CD4+ T cell count of < 300/microliter or < 20% of total T cells on a minimum of two occasions at least 6 weeks apart; no evidence of HIV-1, HIV-2, HTLV-I, or HTLV-II on testing; and the absence of any defined immunodeficiency or therapy associated with decreased levels of CD4+ cells. These patients present with unexplained opportunistic infections. [2] In patients with depressed CD4+ T-lymphocyte counts, other causes should be considered besides HIV infection. Common variable immunodeficiency can present with low CD4+ counts and opportunistic infections but is associated with generally low levels of immunoglobulins [3] differentiating this condition from ICL, in which immunoglobulin levels are usually in the normal range. It is possible that in the case described here cryptococcal infection may have led to the decline in CD4+ cells. It has been suggested that cryptococcal antigens may block cell-mediated immunity through suppressor T-cell function. [4,5] However, it has not been reported previously whether a specific decline in CD4+ levels may be due to cryptococcal antigens.

Isolated osteomyelitis due to infection with C. neoformans is extremely rare. There are approximately 75 reported cases of cryptococcal infections with bone involvement, comprising 5% of all cryptococcal infections. The lumbar spine, pelvis, and ribs are most commonly affected. To date, skull involvement has been reported in a total of 13 cases in the world. [6],[7] Prior reports of cryptococcal infections of the skull have emphasized the radiographic findings of acute osteomyelitis. Specifically, these features include a lytic lesion eroding the inner and outer tables (without surrounding sclerosis), bony sequestrum, and an overlying soft mass. [8] This case demonstrates these features [Figure - 1]. However, such features are not specific for cryptococcus, and other infectious etiologies, especially other fungi, need to be entertained as an appropriate differential diagnosis.

Cryptococcal pyelonephritis has been documented only in transplant recipients and is usually refractory to treatment. The malignancies most commonly causing immunosuppresion are leukemias and lymphomas. Renal cell carcinoma per se is not known to cause immunosuppresion. The association of calvarial cryptococcal osteomyelitis with renal cell carcinoma has not been reported in the literature.

In conclusion, it is imperative to be aware of the atypical presentations of cryptococcal infections, especially in HIV-negative patients. This case highlights the unusual presentation of an adult diabetic male with renal cell carcinoma and transient immunosuppression presenting with cryptococcal osteomyelitis of skull.


1.Chuck SL, Sande MA. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med 1989;321:794-9.  Back to cited text no. 1  [PUBMED]  
2.Cheung MC, Rachlis AR, Shumak SL. A cryptic cause of cryptococcal meningitis. CMAJ 2003;168:451-2.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Sneller MC, Strober W, Eisenstein E, Jaffe JS, Cunningham-Rundles C. New insights into common variable immunodeficiency. Ann Intern Med 1993;188:720-30.   Back to cited text no. 3    
4.Muller J. Immunological aspects of cryptococcosis in AIDS patients. In: Vanden Bossche H, MacKenzie DW, Cauwenbergh G, van Cutsem J, Drouhet E, Dupont B, et al, editors. Mycoses in AIDS patients. New York: Plenum Press; 1990. p. 123-32.   Back to cited text no. 4    
5.Murphy JW. Clearance of Cryptococcus neoformans from immunologically suppressed mice. Infect Immun 1989;57:1946-52.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Armonda RA, Fleckenstein JM, Brandvold B, Ondra SL. Cryptococcal skull infection: A case report with review of the literature. Neurosurgery 1993;32:1034-6.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Amit A, Sudish K, Pople IK. Primary calvarial cryptococcal osteomyelitis in a patient with idiopathic lymphopenia. Acta Neurochir (Wien) 2008;150:713-4.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Galloway DC, Schochet SS. Cryptococcal skull infections. J Neurosurg 1981;54:690-2.  Back to cited text no. 8    

Copyright 2010 - Neurology India

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