Pseudotumor presentation of intracerebral tuberculomas.

Abstract: Diagnosis of tuberculoma is difficult because of its tumorlike aspects. This report describes the case of a male who displayed a hemiplegia revealing an intracranial mass. Neuroimaging was consistent with a glioblastoma; however, the definite diagnosis was a tuberculoma. Clinical features of tuberculomas are nonspecific. Even though the neuroimaging features are sensitive, they are much less specific, with variability related to the tuberculoma course. Investigations leading to the diagnosis are histologic analysis showing a granuloma with or without caseating necrosis, and the microbiologic identification of Mycobacterium tuberculosis. Every intracranial tumor with malignant radiologic and clinical appearance must evoke a suspicion for tuberculoma.

Key Words: cerebral pseudotumor, tuberculoma

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In Western countries, tuberculomas represent 0.5% of intracranial (IC) mass lesions, whereas in developing countries they account for up to 40%. (1) We report on a patient who presented with a cerebral tuberculoma exhibiting the radiologic features of a malignant glioma.

Case Report

A 53-year-old male was admitted for leg weakness, with a proprioceptive deficit. There was no history of foreign travel or tuberculosis. Laboratory evaluations were normal, and human immunodeficiency virus testing was negative. A computed tomography (CT) scan of the head revealed a massive enhancing lesion in the left parietofrontal lobe and many homogeneous areas of patchy enhancement with contrast and mass effect, usually characteristic of a malignant glioma. The magnetic resonance imaging (MRI) was consistent with this hypothesis (Figure).

Because of the worsening symptomatology, corticosteroid therapy was started. The patient showed resolution of symptoms. A stereotactic biopsy was performed. Histologic examination uncovered follicular lesions with epithelioid cells and no caseating necrosis. No organisms were seen on Ziehl-Neilsen, periodic acid-Schiff, and Grocott staining. Samples were not sent for bacteriologic testing. Analysis of cerebrospinal fluid (CSF) was normal. No acid-fast bacilli (AFB) were found in either gastric or bronchoalveolar lavage fluid, CSF, or urine. Extracerebral investigations such as thoracoabdominal CT scan, bronchoalveolar lavage fluid, and bronchoscopy with bronchial biopsy did not reveal evidence of tuberculosis. Thus, neural sarcoidosis was diagnosed and the patient was discharged on corticosteroids (1 mg/kg).

Two months later, he was readmitted with motor deficiency and fever. The cerebral CT scan did not show any worsening lesions. CSF biologic evaluation displayed a high protein concentration of 1.4 g/L, and the AFB smear was negative. The AFB smears of gastric fluid and urine were positive. After corticosteroid and antituberculous chemotherapy, including isoniazid (INH, 5 mg/kg per day), rifampin (10 mg/kg per day), pyrazinamide (20 mg/kg per day) and ethambutol (15 mg/kg per day) for a 3-month duration, the patient made a slow clinical recovery. The cultures of urine, CSF, and sputum yielded Mycobacterium tuberculosis, corroborating the disseminated tuberculosis diagnosis.

Four months later, there was a reappearance of the clinical features related to a paradoxical reaction and leading to neurosurgical excision. Direct histologic examination uncovered AFB, whereas culture remained negative. The medical regimen with INH, rifampin, pyrazinamide, and ethambutol was continued, and amikacin was added 3 times per week. Corticosteroids were maintained. Twelve months after hospital discharge, the patient was still following a three-therapy regimen (INH, rifampin, pyrazinamide). The regimen was then interrupted and replaced by a 6-month course of INH and rifampin with an uneventful follow-up.

Discussion

Tuberculosis of the central nervous system is mainly tuberculous meningitis, tuberculomas (15 to 30%), and, rarely, abscess. (2,3) The clinical features are nonspecific. They can be acute, suggesting a malignant tumor. (3) Conversely, 25 to 85% of patients are asymptomatic. (3-5) Extracerebral locations must be systematically investigated, but isolated tuberculosis of the central nervous system represents 40 to 70% of cases. (3,5) Pulmonary tuberculosis is the main extracranial location associated in 30% of cases. Characteristic radiologic features are found in 25 to 50%.

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Cerebral CT scan has a good sensibility but poor specificity. Tuberculomas are either round or lobulated, solitary or multiple. They can be supratentorial or infratentorial. (5) The CT scan may be that of a low or discreetly high-density solid mass. After contrast, the enhancement may be (1) homogenous, (2) surrounding a low or moderately high-density mass, or (3) an association of these appearances. Calcifications found in 1 to 6% of cases are typical of tuberculous lesion. (6) MRI is more adequate to uncover small-sized lesions or infratentorial lesions. However, MRI findings are also variable and nonspecific.

It is not uncommon (20% of cases in Artico et al (4)) for diagnosis to be established after the histologic examination of a suspicious tumor. Although malignant tumors account for 85% of IC masses, the histologic finding of a tuberculoma is often unexpected. (2,4,7-12) This illustrates how difficult it is to make a diagnosis and why extensive microbiologic analysis including AFB smears should be systematically performed when confronted with an IC mass. One of the main clinical features is the discovery of a histologic granuloma. Caseous necrosis is a major symptom of mycobacterial infection. The acid-fast quality of M tuberculosis allows for rapid detection on a smear with the appropriate staining. The pathologic diagnosis is not absolute, unless evidence of M tuberculosis is found on cultures. CSF analysis is quite often normal, and bacteriologic tests on cerebral samples may remain negative. (13) Identification of mycobacteria through the use of polymerase chain reaction must be mentioned, owing to its good positive predictive value, but it is also limited by a poor negative predictive value.

Cerebral tuberculosis mortality rates range from 5 to 60%. Standard treatment is medical. As a first step, a four-drug therapy is continued for 2 months (INH, rifampin, pyrazinamide, and ethambutol or streptomycin) followed by two-drug therapy (INH, rifampin). Classically, this duration is for 18 months, or until the disappearance of intracerebral lesions or their resolution into a calcification. (14,15) The value of adjuvant corticosteroids is still under evaluation. Under medical regimen alone, the clinical course is for the most part uneventful. As in our case, a paradoxical enlargement, regardless of sufficient serum concentration and lack of antituberculous drug resistance, has been reported, although it is uncommon. (14) At this point, the medical regimen varies, with continuation of medical treatment if no clinical deterioration occurs, adjunction of a new antituberculous drug, addition or increased dose of corticosteroids, or surgical intervention.

Conclusion

Cerebral tuberculoma is a caseous foci with fibrous encapsulation. It presents with clinical aspects of an IC tumor with neurologic deficit and risk of elevated IC pressure. When confronted with an intracerebral mass, the diagnosis of tuberculosis must be considered, even in patients without immunodeficiency and even though clinical and radiologic characteristics are greatly consistent with a malignant tumor. Histologic granuloma often leads to a presumptive diagnosis, but there is no absolute pathologic diagnosis without microbiologic tests, which must be performed systematically, so as not to delay the diagnosis.

Anger and jealousy can no more bear to lose sight of their objects than
love ...
--George Eliot, The Mill on the Floss

Accepted September 21, 2004.

References

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RELATED ARTICLE: Key Points

* Tuberculosis of the central nervous system is primarily either tuberculosis meningitis, tuberculomas (15 to 30%), and, rarely, abscess.

* One of the main clinical features is the discovery of a histologic granulomatous intracranial mass.

* Every intracranial tumor with malignant radiologic and clinical appearance must evoke a suspicion for tuberculoma.

Valerie Chanet, MD, Olivier Baud, MD, Didier Deffond, MD, Jean-Pierre Romaszko, MD, and Jean Beytout, MD

From the Infectious Diseases Department and the Bacteriology Department, Hotel-Dieu, and the Neurology Department, Gabriel-Montpied, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France.

Reprint requests to Dr. Valerie Chanet, Infectious Diseases Department, Hotel-Dieu, University Hospital of Clermont-Ferrand, 63000 Clermont-Ferrand, France. Email: [e-mail]