|Year : 2015 | Volume
| Issue : 3 | Page : 653
Intracranial tuberculoma mimicking brain metastasis
Abhijit L Salaskar, Wael Hassaneen, Cheryl H Keenan, Dima Suki
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
|Date of Web Publication||9-Oct-2015|
Department of Neurosurgery, Unit 442, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd, Houston, Texas - 77030
Source of Support: None, Conflict of Interest: None
To our knowledge, this is the first report of an intracranial tuberculoma in an immunocompetent patient with a solid primary tumor outside the central nervous system. This case is important because the patient underwent treatment for a presumed brain metastasis, based on the knowledge that a solid extracranial primary tumor was present, but before the brain lesion pathology was determined.
Keywords: Brain metastasis, central nervous system, intracranial tuberculomas, tuberculosis
|How to cite this article:|
Salaskar AL, Hassaneen W, Keenan CH, Suki D. Intracranial tuberculoma mimicking brain metastasis. J Can Res Ther 2015;11:653
| > Introduction|| |
In developed countries, about 4% of central nervous system (CNS) lesions are caused by tuberculosis (TB). Accurate diagnosis is the first step in the journey towards a successful patient outcome, but this becomes difficult in the absence of extracranial TB, as seen in the case we report here. Many cases of CNS tuberculoma (CNST) that resemble intracranial tumors on imaging have been reported, but a solid primary tumor (SPT) at diagnosis was absent in all of them, and treatment was postponed until the brain lesion pathology was determined.
| > Case report|| |
A 51-year-old woman complained of a sore under her tongue. She had had difficulty chewing and speaking, with pain in the anterior mandibular teeth area, sore throat, episodic numbness on the left side of the face, neck, tongue, gums, and lip during the preceding month, and a 15-pound weight loss over four months. She denied having fever, chills, night sweats or productive cough. She had a history of heavy ethanol use and 30 packs of cigarettes per year.
A biopsy of the mouth lesion revealed moderate-to-poorly differentiated squamous cell carcinoma (stage T2N1M0). T1-weighted magnetic resonance (MR) images obtained one month after the oral lesion biopsy revealed an edematous gadolinium contrast-enhancing mass (maximal diameter 2.3 cm) in the right cerebellar hemisphere, extending to the tentorium and showing characteristics [Figure 1]a typical of a brain metastasis (BM) [Figure 1]b. The T2-weighted magnetic resonance imaging (MRI) scan showed hypodensity within the center of the mass, with surrounding edema. This was consistent with a necrotic mass with surrounding edema and was also suggestive of a BM. The positron emission tomography (PET) scan revealed fluorodeoxyglucose (FDG)-avid disease in the floor of the mouth and right cerebellum. No MR spectroscopy was performed. The patient had no neurological symptoms in the cerebellar mass diagnosis. She was immunocompetent and tested negative for human immunodeficiency virus (HIV). Headache and ataxia symptoms appeared 20 days after the detection of the mass. Therefore, resection of the probable metastasis was indicated. Preoperative MR imaging showed no change in size.
The neurosurgery was uneventful, the cerebellar mass was completely resected [Figure 1]c, and the patient's neurological symptoms resolved.
|Figure 1: (a) Preoperative contrast-enhanced T1-weighted axial MRI of the brain showing a right cerebellar ring-enhancing lesion resembling a metastatic lesion, (b) Preoperative contrast-enhanced T1-weighted axial MRI of the brain showing a histologically proven brain metastasis in the right cerebellar hemisphere, (c) T1-weighted axial MRI of the brain showing the resection cavity with no evidence of enhancement, (d) Histologic section from the resected cerebellar mass showing multiple granulomas composed of epithelioid histiocytes, lymphocytes, and Langhan's giant cells. (x100 magnification), (e) Gomori methenamine silver (GMS) stain showing round yeast (arrow) of a uniform 5 to 6 micrometers in diameter. The morphology of the microorganisms is consistent with blastomyces a period|
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The resected mass was found to be a necrotizing granuloma [Figure 1]d. There were no malignant cells, but round yeast cells [diameter 5-6 micrometers; [Figure 1]e] were detected, consistent with the presence of blastomyces, prompting treatment with voriconazole. After the diagnosis of blastomycosis, the patient had a chest computer tomography (CT) scan, which was negative, a transthoracic echocardiogram, which was negative for cardiac vegetations, and the subsequent blood cultures were also negative. Follow-up MR images four weeks later showed a new 3 mm enhancing lesion in the left occipital lobe. Although an acid-fast bacillus (AFB) smear with Ehrlich Ziehl-Nelson's staining did not detect acid-fast bacilli in the original resected lesion, a culture from it on the Lowenstein-Jensen medium grew Mycobacterium tuberculosis five weeks later. Reinvestigation of the patient's history revealed close contact with a family member with active TB.
The patient underwent an intensive two-month course of quadruple antituberculosis chemotherapy (isoniazide, rifampin, ethambutol, pyrazinamide), with control of the intracranial TB. Resection of the oral cavity lesion was performed along with bilateral selective cervical lymph node dissection. The MR images obtained six months after antituberculosis chemotherapy initiation showed no evidence of local or distant recurrence of the resected cerebellar lesion and a stable nonenhancing left occipital lesion. Antituberculosis chemotherapy was administered for nine months after CNST diagnosis. Twelve months after the cerebellar mass resection, the patient succumbed to metastases to the trachea, mediastinum, and lung.
| > Discussion|| |
Central nervous system involvement occurs in 10-15% of the patients with TB. Tuberculous meningitis is the most frequent manifestation of CNS TB, followed by CNST and tuberculous abscess. CNSTs constitute approximately 4% of the intracranial masses seen in developed countries and 15-30% of those in developing countries. They are usually solitary, with 15-34% being multiple.
Often, the findings of a primary TB infection are absent. Our patient showed no fever, chills, night sweats or productive cough. CNST is challenging to diagnose, because it mimics other infectious and noninfectious medical conditions, especially in asymptomatic patients. Moreover, its imaging characteristics with CT and MR imaging resemble those of other intracranial focal lesions. As assessed by CT morphology alone, a solitary CNST may be indistinguishable from an abscess (pyogenic or fungal), a tumor or another ring-enhancing lesion.
Magnetic resonance imaging findings of CNST depend on whether the tuberculoma is caseating or noncaseating. A solid caseating granuloma may appear isointense or hypointense on T1-weighted MR images and hypointense on T2-weighted images - a hypointensity that corresponds with solid caseation necrosis [Figure 1]b, and these lesions typically show ring enhancement.  Noncaseating granulomas appear hypointense on T1-weighted MR images and hyperintense on T2-weighted MR images,  but there is considerable overlap with other intracranial focal lesions (e.g., fungal granulomas, primary, and metastatic neoplasms). Caseating and fungal granulomas have high iron and manganese levels, causing hypointensity on T2-weighted MR images. However, they can be differentiated based on different resonance patterns using in vivo proton MR spectroscopy. 
Positron emission tomography (PET) was used to identify FDG-avid disease in the floor of the mouth and cerebellum, supporting a diagnosis of BM rather than CNST. Nevertheless, FDG is not a cancer-specific agent, and intense uptake of FDG may occur on PET scans in patients having infectious diseases (mycobacteria, fungi, bacteria), sarcoidosis or radiation pneumonitis. In contrast, adenomas, broncholoalveolar carcinomas, carcinoid tumors, low-grade lymphomas, and small tumors have low glycolytic activity, leading to false-negative results on PET scans. 
Even as the AFB smear failed to detect acid-fast bacillus, the culture for M. tuberculosis was positive after five weeks, leading to a final diagnosis of tuberculoma. As the number of bacilli the CNST varied with the degree of immunosuppression, the patient's immunocompetent status could explain the negative result of the AFB smear.
The patient developed headache and ataxia one month after detection of the suspected Resection was performed to relieve the intracranial pressure. Had she been asymptomatic, based on the brain mass size, she probably would have undergone stereotactic radiosurgery, unnecessarily exposing her to radiation side effects.
Central nervous system tuberculoma, although rare, must be included in the differential diagnosis when an intracranial mass is detected, even when an extracranial solid primary tumor is noted. If a patient's clinical presentation includes risk factors/conditions for TB, such as human immunodeficiency virus (HIV) infection, intravenous drug use, alcohol use, aggressive chemotherapy, transplantation, active TB contact, or overcrowding, there may be a reason to suspect CNST. In our study, CNST was not suspected because the patient was immunocompetent and lacked TB symptoms, although the presence of an active TB family contact and her history of heavy alcohol use should have been illuminating.
In asymptomatic patients in whom an intracranial mass is highly suspected of being non neoplastic, stereotactic biopsy is preferred because of its 85% diagnostic efficacy when followed by paraffin sectioning and histopathological examination.  This less invasive method may prevent misdiagnosis of the lesion as a BM, mitigating the need for unnecessary treatments like radiotherapy. Once a CNST diagnosis is confirmed, conventional antituberculosis chemotherapy is the preferred treatment. Resection must be reserved for cases with symptomatic CNST and antituberculosis chemotherapy failure.
| > Acknowledgment|| |
The authors would like to acknowledge Dr. David Wildrick for editorial assistance.
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