Intracerebral tuberculoma misdiagnosed as neurosarcoidosis. (Case Report).

Abstract: We describe two patients who had tuberculomas that were initially misdiagnosed as neurosarcoidosis, leading to prolonged steroid therapy before initiation of antituberculous medications. Neither patient was infected with the human immunodeficiency virus, and one of the patients had a negative tuberculosis skin test.

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Key Points

* Intracranial tuberculomas may be misdiagnosed as neurosarcoidosis.

* Intracranial tuberculomas should be ruled out before initiating steroid therapy.

* Smears and cultures for acid-fast bacilli are often unrevealing in patients with intracranial tuberculomas.

* Brain biopsy should be sent for acid-fast bacillus smear and culture, and possibly for Mycobacterium tuberculosis polymerase chain reaction, in any patient with granulomatous changes seen on pathologic examination.

* It may be difficult to differentiate the magnetic resonance imaging (MRI) findings of patients with tuberculomas from those of patients with other infective (fungal or bacterial brain abscess, toxoplasmosis, or cysticercosis), inflammatory (sarcoidosis), or malignant (lymphoma) lesions.

Tuberculosis incidence has increased significantly worldwide and controlling multidrug resistant Mycobacterium tuberculosis is a global public health priority. Hematogenous spread to the meninges and other organs occurs early in the course of infection. (1) Fifteen to 20% of extrapulmonary tuberculosis (TB) cases involve the central nervous system (CNS), manifesting as meningitis, cerebritis, tuberculomas, or tubercular abscesses. (2) Intracranial tuberculomas are rare, accounting for 0.2% of intracranial space-occupying lesions. (3) The radiologic findings are often nonspecific, and they are difficult to diagnose without an increased index of suspicion. We describe two cases of intracerebral tuberculomas in patients testing negative for human immunodeficiency virus (HIV) who were misdiagnosed as having neurosarcoidosis.

Discussion

Tuberculomas have a central zone of caseation necrosis surrounded by a capsule containing few bacilli. Fewer than half of patients with tuberculomas have a known history of TB. (4) The tuberculin skin test is positive in up to 85% of patients with tuberculomas, and a chest x-ray suggestive of TB is seen in 30 to 80% of patients. (4) Cerebrospinal fluid has an elevated protein level; AFB smear and cultures are usually negative. Neuroradiologic studies reveal parenchymal disease, commonly involving the corticomedullary junction and periventricular regions, consistent with hematogenous spread of infection. On CT scan, tuberculomas are peripheral, hypodense, ring-enhancing lesions, at times with central calcification, the so-called target sign.5 Tuberculomas are isointense on [T.sub.1]-weighted MRI images. On [T.sub.2]-weighted images, noncaseating lesions are bright with nodular enhancement, while caseating tuberculomas vary from isointense to hypointense and also exhibit ring enhancement. (5) It may be diffic ult to differentiate the MRI findings of patients with other infective (fungal or bacterial brain abscess, toxoplasmosis, or cysticercosis), inflammatory (sarcoidosis), or malignant (lymphoma) lesions.

Intracerebral tuberculomas are uncommon, and neuroradiological findings are often nonspecific. A working diagnosis of neurosarcoidosis in the cases described above led to prolonged steroid therapy and delayed the correct diagnosis and treatment. A detailed history and strong clinical suspicion are important in directing appropriate studies necessary to diagnose this potentially life-threatening, but treatable disease. Intracranial tuberculomas should be ruled out before initiating steroid therapy for suspected neurosarcoidosis, or antituberculous therapy should be initiated after appropriate cultures are obtained in cases where steroid therapy is imperative. In addition to routine pathologic examination, biopsy specimens must be sent to the microbiology laboratory for AFB smear and culture in enigmatic cases and in cases of suspected neurosarcoidosis. Pathologists should be contacted to discuss such cases so that appropriate special stains of the biopsy material are done. This is especially important in conf using cases involving noncaseating granulomas, which are typical of sarcoidosis but may also be seen in tuberculosis. Since AFB smears of tuberculomas are often unrevealing, molecular methods such as polymerase chain reaction (PCR) may be necessary to aid in the diagnosis. (6) With optimal therapy, tuberculomas may resolve completely in 6 months. (7)

Conclusions

We have described two patients who had tuberculomas misdiagnosed as neurosarcoidosis. The diagnosis of tuberculoma requires a high index of suspicion, and the condition can be confused with neurosarcoidosis because cerebrospinal fluid MB smear and cultures are usually negative and the results of neuroradiographic studies are not pathognomonic. An aggressive workup for the diagnosis of a tuberculoma should be pursued before initiating steroid therapy for patients with presumed neurosarcoidosis, especially those who have a positive TB skin test.

Accepted January 15, 2002.

References

(1.) Rich AR, McCordock HA. Pathogenesis of tuberculous meningitis. Bull Johns Hopkins Hosp 1933;52:5-37.

(2.) Udani PM, Parekh UC, Dastur DK. Neurological and related syndromes in CNS tuberculosis: Clinical features and pathogenesis. J Neurol Sci 1971; 14:341-357.

(3.) Artico M, De Caro GM, Carloia S, Salvati M, D'Ambrosio M, Delfini R. Advances in diagnosis, treatment and prognosis of intracerebral tuberculomas in the last 50 years: Report of 21 cases. Neurochirurgie 1999;45:129-133.

(4.) Harder E, AI-Kawi MZ, Carney P. Intracranial tuberculoma: Conservative management. Am J Med 1983;74:570-576.

(5.) Whiteman ML. Neuroimaging of central nervous system tuberculosis in HIV-infected patients. Neuroimaging Clin N Am 1997;7:199-214.

(6.) Ikonomopoulos JA, Gorgoulis VG, Zacharatos PV, Manolis EN, Kanavaros P, Rassidakis A, et al. Multiplex polymerase chain reaction for the detection of mycobacterial DNA in cases of tuberculosis and sarcoidosis. Mod Pathol 1999;12:854-862.

(7.) DeAngelis LM. Intracranial tuberculoma: Case report and review of literature. Neurology 1981;31:133-1136.

RELATED ARTICLE: Case Report

Case 1

A 70-year-old woman, originally from West Virginia, was admitted to a local hospital with difficulty ambulating, chronic headaches, confusion, and low back pain. A computed tomographic (CT) scan demonstrated multiple cerebral lesions. She was an alcoholic and former smoker. Her temperature upon admission to our hospital was 97[degrees]F. She was aphasic and unable to ambulate. Chest x-ray demonstrated a right-sided pleural effusion and pleural thickening. The patient underwent stereotactic brain biopsy, which revealed granulomatous inflammation with reactive gliosis. The specimen was not sent for special stains or cultures. Dexamethasone therapy was begun for suspected neurosarcoidosis. She developed right-sided focal seizures and fever. Magnetic resonance imaging (MRI) revealed extensive edema at the right caudate head, right anterior limb of the internal capsule, and left frontoparietal junction. A hypodensity was also noted, most likely representing a prior infarction. The corticosteroid dose was increased . A purified protein derivative (tuberculin) (PPD) had 16 mm induration, and the patient was given isoniazid for presumed latent tuberculosis. A cervical lymph node biopsy revealed granulomatous lymphadenitis with a histopathologic pattern compatible with sarcoidosis. The specimen was not sent for culture. The patient had a positive rapid plasma reagin (RPR) and positive serum and cerebrospinal fluid (CSF) fluorescent treponemal antibody absorption (FTA-ABS) tests, and she received treatment for neurosyphilis. The HJV serology was negative.

Histopathologic examination of left pleural fine-needle aspiration and biopsy specimens showed no evidence of neoplasm. Microbiologic cultures were sent for evaluation of this specimen. The MRI was repeated and revealed complete effacement of the right frontal horn, with increasing vasogenic edema extending into right midbrain, significant brainstem compromise, and impending risk of uncal herniation. Dosage of corticosteroids was again increased.

Urine and pleural-biopsy acid-fast bacillus (AFB) cultures were positive for Mycobacterium tuberculosis, and the patient was treated with isoniazid, rifampin, pyrazinamide, and ethambutol. The isolate was found to be susceptible to all antituberculosis drugs tested, and ethambutol was discontinued. The patient continued treatment for 13 months. She survived but with severe neurologic impairment.

Case 2

A 52-year-old previously healthy man, originally from the Dominican Republic, was admitted with new onset of seizures and headache. He had no fever on admission or afterward. A CT scan revealed enhancing parietal lobe lesions and associated edema (Fig. 1). Chest x-ray was unrevealing. His HIV serology was negative. Stereotactic brain biopsy revealed granulomatous encephalitis. The lesion consisted of noncaseating granulomas. The pathology report stated that the lesions were commonly seen in sarcoidosis. Bacterial, fungal, and AFB stains and cultures were negative. The patient was treated with high-dose steroids for a working diagnosis of neurosarcoidosis. A PPD test was negative. After tapering the steroid dose, PPD test was repeated and was again negative. Follow-up CT scan demonstrated a small, enhancing lesion in the left parietal region with less surrounding edema than in the previous CT scan.

The patient developed headache and nausea. An MRI revealed the previous lesions to be enlarged. His neurologic status worsened and he underwent an emergent craniotomy. The gross surgical findings were consistent with an abscess, which was drained. An AFB smear was positive, and the patient was started on isoniazid, pyrazinamide, rifampin, and ethambutol. He developed uncal hemiation and died. Mycobacterium tuberculosis grew from the surgical specimen and was susceptible to all antituberculous drugs tested.

From the Division of Clinical Mycology and the Laboratory of Immunoregulation, National Institutes of Allergy, Immunology, and Infectious Diseases, National Institutes of Health, Bethesda, MD; and the Division of Infectious Diseases, Brown University School of Medicine and Rhode Island Hospital, Providence, RI.

Reprint requests to Leonard A. Mermel, DO, ScM, Division of Infectious Diseases, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903. Email: [e-mail]

Copyright [c] 2003 by The Southern Medical Association 003 8-4348/03/9605-0494