![PET-CT of a tuberculoma](https://upload.wikimedia.org/wikipedia/commons/6/69/PET-CT_of_a_tuberculoma.png)
A tuberculoma is a clinical manifestation of
tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, i ...
which conglomerates
tubercle
In anatomy, a tubercle (literally 'small tuber', Latin for 'lump') is any round nodule, small eminence, or warty outgrowth found on external or internal organs of a plant or an animal.
In plants
A tubercle is generally a wart-like projection ...
s into a firm lump, and so can mimic
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s of many types in
medical imaging studies. They often arise within individuals in whom a primary tuberculosis infection is not well controlled.
When tuberculomas arise intracranially, they represent a manifestation of CNS tuberculosis.
Since these are evolutions of
primary complex, the tuberculomas may contain
caseum or
calcification
Calcification is the accumulation of calcium salts in a body tissue. It normally occurs in the formation of bone, but calcium can be deposited abnormally in soft tissue,Miller, J. D. Cardiovascular calcification: Orbicular origins. ''Nature Ma ...
s.
With the passage of time, ''
Mycobacterium tuberculosis'' can transform into crystals of
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...
. These can affect any organ such as the brain, intestine, ovaries, breast, lungs, esophagus, pancreas, bones, and many others. Even with guideline-directed treatment they often persist for months to years.
Mechanism
The exact mechanism of tuberculoma development has not been determined, although multiple theories have been proposed. It is possible that, following an initial tuberculosis infection resulting in
bacteremia, a foci of
granulomatous inflammation
A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious o ...
may coalesce into a
caseous
Caseous necrosis or caseous degeneration () is a unique form of cell death in which the tissue maintains a cheese-like appearance.Robbins and Cotran: Pathologic Basis of Disease, 8th Ed. 2010. Pg. 16 It is also a distinctive form of coagulative nec ...
tuberculoma.
Pulmonary tuberculomas may arise due to repeated cycles of necrosis and re-encapsulation of foci, or, alternatively, the shrinkage and fusion of encapsulated densities.
In regards to CNS tuberculoma, it is thought that mycobacterium tuberculosis is capable of penetrating the
blood brain barrier
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
after bacterial bacilli induce the release of
cytokines by various immunologic cells, leading to an increase in barrier permeability.
Similar to pulmonary tuberculomas, small lesions eventually coalesce and undergo both necrosis and enlargement.
Signs and symptoms
Symptoms are based on the location of the tuberculoma. Small, scattered lesions may be asymptomatic. Intracranial tuberculomas in children are often infratentorial, occurring near the
cerebellum and base of the brain. In this population, symptoms such as headache, fever, focal neurologic findings and seizures have been seen
in addition to
papilledema
Papilledema or papilloedema is optic disc swelling that is caused by increased intracranial pressure due to any cause. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare.
In ...
with or without
meningitis.
When the size of a brainstem tuberculoma grows to the point of narrowing the
fourth ventricle
The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ve ...
,
obstructing hydrocephalus and its related symptoms can arise.
Rupture of tuberculomas adjacent to the arachnoid can lead to
arachnoiditis
Arachnoiditis is an inflammatory condition of the arachnoid mater or 'arachnoid', one of the membranes known as meninges that surround and protect the nerves of the central nervous system, including the brain and spinal cord. The arachnoid can be ...
,
while rupture near the subarachnoid space or ventricular system can cause meningitis.
Diagnosis
![Tuberculosis - Tuberculoma with cavitation (6596009867)](https://upload.wikimedia.org/wikipedia/commons/e/e0/Tuberculosis_-_Tuberculoma_with_cavitation_%286596009867%29.jpg)
The diagnosis of tuberculoma can be challenging, as invasive testing may be required and, occasionally, concomitant malignancy may be present.
In children with tuberculoma, CXR is often normal despite a positive TST/
IGRA
Igra (russian: Игра; udm, Эгра, ''Egra'') is a rural locality (a settlement) and the administrative center of Igrinsky District of the Udmurt Republic, Russia, located north of Izhevsk at the European route E22, which changes there f ...
.
Diagnosis of brain tuberculoma can be aided with
PCR of
cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...
, but is of less utility for quickly diagnosing and treating lesions.
When CSF is analyzed in patients with suspected tuberculoma, high protein concentrations are cell counts are often seen.
Definitive diagnosis can be made through
stereotactic, CT-guided biopsy, with excision required in rare cases. Biopsy is chosen when non-invasive testing has failed to produce a diagnosis, when patients fail to respond to a treatment regimen, in cases of drug-resistant tuberculosis, and in non-compliant patients.
Imaging
The appearance of a tuberculoma on imaging can vary according to the composition and age of the mass. They may appear as either non-caseating or solidly
caseating
Caseous necrosis or caseous degeneration () is a unique form of cell death in which the tissue maintains a cheese-like appearance.Robbins and Cotran: Pathologic Basis of Disease, 8th Ed. 2010. Pg. 16 It is also a distinctive form of coagulative nec ...
lesions.
Initially, tuberculomas appear
hypodense on computed tomography (CT) scans with significant surrounding edema.
The "target sign" is
pathognomonic Pathognomonic (rare synonym ''pathognomic'') is a term, often used in medicine, that means "characteristic for a particular disease". A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doub ...
for tuberculoma on CT, with a nodular
ring-enhancing mass and central calcification.
The characteristic ring-enhanced appearance is due to lack of blood supply in the central necrotic core that is visualized with
injected contrast.
Sometimes a hypodense central area is seen instead of calcification. When considering other potential intracranial masses in a differential diagnosis, such as
cysticercosis
Cysticercosis is a tissue infection caused by the young form of the pork tapeworm. People may have few or no symptoms for years. In some cases, particularly in Asia, solid lumps of between one and two centimetres may develop under the skin. Aft ...
,
pyogenic
Pus is an exudate, typically white-yellow, yellow, or yellow-brown, formed at the site of inflammation during bacterial or fungal infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collection ...
abscess, and
neoplastic
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
lesions, tuberculoma can be identified by its larger size (>2 cm), edema, and irregular border.
Magnetic resonance imaging (MRI) is another useful imaging modality for diagnosing and characterizing of tuberculomas, especially solid caseous necrosis in which 3 zones of varying intensity are seen.
Treatment
Tuberculoma is commonly treated through the
HRZE drug combination (
Isoniazid
Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For la ...
,
Rifampin
Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used tog ...
,
Pyrazinamide
Pyrazinamide is a medication used to treat tuberculosis. For active tuberculosis, it is often used with rifampicin, isoniazid, and either streptomycin or ethambutol. It is not generally recommended for the treatment of latent tuberculosis. I ...
,
Ethambutol
Ethambutol (EMB, E) is a medication primarily used to treat tuberculosis. It is usually given in combination with other tuberculosis medications, such as isoniazid, rifampicin and pyrazinamide. It may also be used to treat ''Mycobacterium avi ...
) followed by maintenance therapy.
Per international guidelines, 9–12 months of medical management is standard.
While the majority of tuberculomas resolve in 12–24 months, in patients with multiple or larger lesions prolonged treatment extending beyond two years may be required. In some patients, the release of inflammatory mediators during treatment can cause a paradoxical worsening of symptoms that is treated with
anti-inflammatory medications in addition to the standard anti-tuberculosis regimen.
Exceptionally large tuberculomas, those exerting a mass effect on the brain, and those which fail to respond to medical management required surgical excision. In some cases, surgical excision is necessary for diagnosis as well as treatment.
When intracranial pressure rises in the setting of tuberculoma, removal is considered a surgical emergency.
Prognosis
Of patients with a brain tuberculoma treated with an appropriate medication regimen, almost half recover completely. Approximately 10% of those treated fail to recover and succumb to the tuberculoma.
Reports issued before the advent of effective anti-tuberculosis therapy showed that, when untreated, 30-50% of tuberculomas enter and remain in a stationary course.
Epidemiology
Tuberculomas are most commonly seen in areas where tuberculosis is
endemic
Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found else ...
. In these areas, tuberculomas can account for between 30%-50% of intracranial masses.
India and parts of Asia are two areas where tuberculomas have been noted to be particularly prevalent.
They occur most often as solitary,
infratentorial
In anatomy, the infratentorial region of the brain is the area located below the tentorium cerebelli. The area of the brain above the tentorium cerebelli is the supratentorial region. The infratentorial region contains the cerebellum
The cerebe ...
lesions in young children.
In contrast, lesions are most often
supratentorial In anatomy, the supratentorial region of the brain is the area located above the tentorium cerebelli. The area of the brain below the tentorium cerebelli is the infratentorial region. The supratentorial region contains the cerebrum, while the infr ...
in adults.
Pulmonary tuberculomas are among the most common benign nodules, with 5%-24% of all resected nodules being of tuberculous origin.
In areas of lower prevalence, such as the United States, they are most commonly seen in the setting of an
acquired immunodeficiency.
Intracerebral tuberculomas, specifically, are more frequently observed in patients with an
HIV infection
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...
.
References
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Tuberculosis
Lesion
Pulmonary lesion